silicon and Neoplasms

The review covers some research conducted in the field of medical and biomedical application of devices based on silicon sensor elements (Si-NW-sensors). The use of Si-NW-sensors is one of the key methods used in a whole range of healthcare fields. Their biomedical use is among the most important ones as they offer opportunities for early diagnosis of oncological pathologies, for monitoring the prescribed therapy and for improving the people's quality of life.

Topics: Biosensing Techniques; Early Detection of Cancer; Humans; Nanowires; Neoplasms; Quality of Life; Silicon

The plant pentacyclic alkaloid camptothecin and its structural analogs were extensively studied. These compounds are interesting due to the antitumor activity associated with their ability to inhibit topoisomerase I in tumor cells. During the last decades of the 20th century, a large number of the silicon-containing camptothecins (silatecans) were synthesized. 7-tert-Butyldimethylsilyl-10-hydroxy-camptothecin (DB-67 or AR-67) has enhanced lipophilicity and demonstrates a antitumor activity superior to its carbon analog. To date, certain silatecans are under clinical trials and their ultimate role in cancer therapy appears promising. In this review, we present chemical methodologies for the synthesis of silicon-containing camptothecins, their chemical properties, biological activity, and results of clinical trials.

Topics: Animals; Antineoplastic Agents, Phytogenic; Camptothecin; Cell Proliferation; Humans; Molecular Structure; Neoplasms; Silicon

In the past two decades, porous silicon (PSi) has attracted increasing attention for its potential biomedical applications. With its controllable geometry, tunable nanoporous structure, large pore volume/high specific surface area, and versatile surface chemistry, PSi shows significant advantages over conventional drug carriers. Here, an overview of recent progress in the use of PSi in drug delivery and cancer immunotherapy is presented. First, an overview of the fabrication of PSi with various geometric structures is provided, with particular focus on how the unique geometry of PSi facilitates its biomedical applications, especially for drug delivery. Second, surface chemistry and modification of PSi are discussed in relation to the strengthening of its performance in drug delivery and bioimaging. Emerging technologies for engineering PSi-based composites are then summarized. Emerging PSi advances in the context of cancer immunotherapy are also highlighted. Overall, very promising research results encourage further exploration of PSi for biomedical applications, particularly in drug delivery and cancer immunotherapy, and future translation of PSi into clinical applications.

Topics: Drug Delivery Systems; Humans; Immunotherapy; Neoplasms; Porosity; Silicon

The emergence of nanotechnology suggests new and exciting opportunities for early diagnosis and therapy of cancer. During the recent years, silicon-based nanomaterials featuring unique properties have received great attention, showing high promise for myriad biological and biomedical applications. In this review, we will particularly summarize latest representative achievements on the development of silicon nanostructures as a powerful platform for cancer early diagnosis and therapy. First, we introduce the silicon nanomaterial-based biosensors for detecting cancer markers (e.g., proteins, tumor-suppressor genes and telomerase activity, among others) with high sensitivity and selectivity under molecular level. Then, we summarize in vitro and in vivo applications of silicon nanostructures as efficient nanoagents for cancer therapy. Finally, we discuss the future perspective of silicon nanostructures for cancer diagnosis and therapy.

Topics: Animals; Biosensing Techniques; Drug Carriers; Equipment Design; Humans; Nanomedicine; Nanostructures; Neoplasms; Silicon

Semiconductor nanoparticles (or quantum dots, QDs) exhibit unique optical and electronic properties such as size-controlled fluorescence, high quantum yields, and stability against photobleaching. These properties allow QDs to be used as optical labels for multiplexed imaging and in drug delivery detection systems. Luminescent silicon QDs and surface-modified silicon QDs have also been developed as potential minimally toxic fluorescent probes for bioapplications. Silicon, a well-known power electronic semiconductor material, is considered an extremely biocompatible material, in particular with respect to blood. This review article summarizes existing knowledge related to and recent research progress made in the methods for synthesizing silicon QDs, as well as their optical properties and surface-modification processes. In addition, drug delivery systems and in vitro and in vivo imaging applications that use silicon QDs are also discussed.

Topics: Animals; Biocompatible Materials; Drug Carriers; Humans; Neoplasms; Quantum Dots; RNA, Small Interfering; Silicon; Spectroscopy, Near-Infrared

Silicon nanomaterials are an important class of nanomaterials with great potential for technologies including energy, catalysis, and biotechnology, because of their many unique properties, including biocompatibility, abundance, and unique electronic, optical, and mechanical properties, among others. Silicon nanomaterials are known to have little or no toxicity due to favorable biocompatibility of silicon, which is an important precondition for biological and biomedical applications. In addition, huge surface-to-volume ratios of silicon nanomaterials are responsible for their unique optical, mechanical, or electronic properties, which offer exciting opportunities for design of high-performance silicon-based functional nanoprobes, nanosensors, and nanoagents for biological analysis and detection and disease treatment. Moreover, silicon is the second most abundant element (after oxygen) on earth, providing plentiful and inexpensive resources for large-scale and low-cost preparation of silicon nanomaterials for practical applications. Because of these attractive traits, and in parallel with a growing interest in their design and synthesis, silicon nanomaterials are extensively investigated for wide-ranging applications, including energy, catalysis, optoelectronics, and biology. Among them, bioapplications of silicon nanomaterials are of particular interest. In the past decade, scientists have made an extensive effort to construct a silicon nanomaterials platform for various biological and biomedical applications, such as biosensors, bioimaging, and cancer treatment, as new and powerful tools for disease diagnosis and therapy. Nonetheless, there are few review articles covering these important and promising achievements to promote the awareness of development of silicon nanobiotechnology. In this Account, we summarize recent representative works to highlight the recent developments of silicon functional nanomaterials for a new, powerful platform for biological and biomedical applications, including biosensor, bioimaging, and cancer therapy. First, we show that the interesting photoluminescence properties (e.g., strong fluorescence and robust photostability) and excellent biocompatibility of silicon nanoparticles (SiNPs) are superbly suitable for direct and long-term visualization of biological systems. The strongly fluorescent SiNPs are highly effective for bioimaging applications, especially for long-term cellular labeling, cancer cell detection, and tumor im

Topics: Biocompatible Materials; Biosensing Techniques; Diagnostic Imaging; Fluorescent Dyes; Humans; Nanostructures; Nanowires; Neoplasms; Silicon; Spectrum Analysis, Raman

Biomedical applications of porous silicon include drug delivery, imaging, diagnostics and immunotherapy. This review summarizes new silicon particle fabrication techniques, dynamics of cellular transport, advances in the multistage vector approach to drug delivery, and the use of porous silicon as immune adjuvants. Recent findings support superior therapeutic efficacy of the multistage vector approach over single particle drug delivery systems in mouse models of ovarian and breast cancer. With respect to vaccine development, multivalent presentation of pathogen-associated molecular patterns on the particle surface creates powerful platforms for immunotherapy, with the porous matrix able to carry both antigens and immune modulators.

Topics: Animals; Antineoplastic Agents; Blood Proteins; Drug Delivery Systems; Immunotherapy; Neoplasms; Porosity; Silicon; Solubility

Positron emission tomography (PET) plays important roles in cancer diagnosis and molecular imaging research; but potential points remain for which big improvements could be made, including resolution, sensitivity and costs. For example, the sensitivity of present PET scanners does not exceed 10%. This means that more than 90% of the gamma-rays emitted from a subject are not utilized for imaging. Therefore, research on next generation PET technologies remains a hot topic worldwide. In this paper, we introduce some research trends by describing PET physics research in the National Institute of Radiological Sciences (NIRS). A depth-of-interaction (DOI) detector, for which various methods have been studied, will be a key device to get any significant improvement in sensitivity while maintaining high spatial resolution. DOI measurement also has a potential to expand PET application fields because it allows for more flexible detector arrangement. As an example, we are developing the world's first, open-type PET geometry "OpenPET", which is expected to lead to PET imaging during treatment. The DOI detector itself continues to evolve with the help of recently developed semiconductor photodetectors, often referred to as silicon photomultipliers (SiPMs). We are developing a SiPM-based DOI detector to achieve sub-mm spatial resolution, which is reaching the theoretical limitation of PET imaging.

Topics: Animals; Equipment Design; Heavy Ion Radiotherapy; Humans; Image Enhancement; Neoplasms; Photons; Positron-Emission Tomography; Radiotherapy, Image-Guided; Semiconductors; Silicon

Over the past decade, silicon nanowire (SiNW) biosensors have been studied for the detection of biological molecules as highly sensitive, label-free, and electrical tools. Herein we present a comprehensive review about the fabrication of SiNW biosensors and their applications in disease diagnostics. We discuss the detection of important biomarkers related to diseases including cancer, cardiovascular diseases, and infectious diseases. SiNW biosensors hold great promise to realize point-of-care (POC) devices for disease diagnostics with potential for miniaturization and integration.

Topics: Biomarkers, Tumor; Biosensing Techniques; Cardiovascular Diseases; Communicable Diseases; Diagnostic Equipment; Humans; Influenza A Virus, H1N1 Subtype; MicroRNAs; Nanowires; Neoplasms; Silicon; Troponin T

Porous Si exhibits a number of properties that make it an attractive material for controlled drug delivery applications: The electrochemical synthesis allows construction of tailored pore sizes and volumes that are controllable from the scale of microns to nanometers; a number of convenient chemistries exist for the modification of porous Si surfaces that can be used to control the amount, identity, and in vivo release rate of drug payloads and the resorption rate of the porous host matrix; the material can be used as a template for organic and biopolymers, to prepare composites with a designed nanostructure; and finally, the optical properties of photonic structures prepared from this material provide a self-reporting feature that can be monitored in vivo. This paper reviews the preparation, chemistry, and properties of electrochemically prepared porous Si or SiO2 hosts relevant to drug delivery applications.

Topics: Animals; Biocompatible Materials; Delayed-Action Preparations; Drug Delivery Systems; Electrochemistry; Humans; Neoplasms; Porosity; Silicon; Silicon Dioxide

In this chapter various facets of and approaches to systems biology will be discussed. This then leads to an illustration of how systems biology may be used in drug target design. We present five new paradigms for drug target research and show how these are based in systems biology.

Topics: Chemistry, Pharmaceutical; Drug Design; Drug Industry; Extracellular Signal-Regulated MAP Kinases; Humans; Models, Theoretical; Neoplasms; Oscillometry; Phosphorylation; RNA; Silicon; Stochastic Processes; Systems Biology

Optical imaging technique has strong potential for sensitive cancer diagnosis, particularly at the early stage of cancer development. This is a sensitive, non-invasive, non-ionizing (clinically safe) and relatively inexpensive technique. Cancer imaging with optical technique however greatly relies upon the use of sensitive and stable optical probes. Unlike the traditional organic fluorescent probes, fluorescent nanoparticle probes such as dye-doped nanoparticles and quantum dots (Qdots) are bright and photostable. Fluorescent nanoparticle probes are shown to be very effective for sensitive cancer imaging with greater success in the cellular level. However, cancer imaging in an in vivo setup has been recently realized. There are several challenges in developing fluorescent nanoparticle probes for in vivo cancer imaging applications. In this review, we will discuss various aspects of nanoparticle design, synthesis, surface functionalization for bioconjugation and cancer cell targeting. A brief overview of in vivo cancer imaging with Qdots will also be presented.

Topics: Diagnostic Imaging; Fluorescent Dyes; Humans; Microscopy, Fluorescence; Molecular Probe Techniques; Nanotechnology; Neoplasms; Polymers; Quantum Dots; Silicon

Despite the knowledge of the link between many sites of cancer occurence and previous occupational exposure, occupational cancers are generally underestimated. These cancers can be prevented through specific plans. In France, the number of cases requesting and receiving compensation for occupational cancer is increasing. The frequency of occupational exposure to carcinogens was recently evaluated. Legislation was reinforced in order to obtain a better control of exposure to carcinogens in the workplace. Lung cancer is the most frequent of occupational cancers. Epidemiological studies contribute to a better knowledge of etiologies and occupations responsible for the outcome of these cancers and allow quantification of the risk of cancer linked to different situations of exposure. Beside classical epidemiological studies, molecular epidemiology aims at identifying molecular targets of occupational agents. This approach may allow a better knowledge of the part played by occupational agents in these multifactorial diseases.

Topics: Electromagnetic Fields; France; Humans; Lung Neoplasms; Mineral Fibers; Neoplasms; Occupational Diseases; Occupational Exposure; Occupational Health; Occupations; Risk Factors; Silicon

DNA chips are miniaturized microsystems based on the ability of DNA to spontaneously find and bind its complementary sequence in a highly specific and reversible manner, known as hybridization. Labeled DNA molecules in a sample are analyzed by DNA probes tethered at distinct sites on a solid support. The composition of the DNA sample is then deduced by analyzing the signal generated by labels present at each probe site. Applications are widespread: fundamental research, cancer or microbiology diagnostics, genotyping, gene expression, pharmacogenomics, and environmental control. Medical application consists, for example, in the identification and detection of mutations in genes responsible for cancers, or DNA chip analysis of individual polymorphisms which may provide a guide towards the most efficient treatment. In the environmental and agro-industrial fields, DNA chips show great promise in rapidly testing microorganism content, contamination or pathogenicity. DNA chip dimensions offer hybridization sites in the 50-200 micron range, producing arrays ranging from 100 to 1,000,000 different probes per cm2.

Topics: DNA Probes; DNA, Neoplasm; Equipment Design; Gene Expression Profiling; Genes, ras; Genotype; Gold; Humans; Microelectrodes; Neoplasms; Oligonucleotide Array Sequence Analysis; Silicon

Having briefly analyzed the role of silicon specially in the metabolism of connective and bone tissue, the author describes conditions induced by silicon deficit and poisoning due to this metal. The most recent findings concerning the role of silicon in delaying the onset and reducing the extension of atherosclerotic processes are also illustrated.

Topics: Aging; Animals; Arteriosclerosis; Humans; Neoplasms; Silicon

Consideration of the human epidemiology of diseases arising from exposure to naturally occurring and man-made mineral fibers encompasses the several forms of asbestos (chrysotile, crocidolite, amosite, anthophyllite, tremolite-actinolite), other naturally occurring silicates (talc, sepiolite, erionite, attapulgite, vermiculite, and wollastonite), and man-made mineral fibers (glass continuous filament, glass/rock/slag insulation wools, ceramic and other refractory fibers, and glass microfibers). The diseases arising from exposures to some of these fibers include pleural thickening (plaques, diffuse pleural thickening, and calcification), pulmonary fibrosis, lung cancers, mesothelioma of the pleura and peritoneum, and other cancers). Risk factors important in assessing these diseases include assessment of latency, duration of exposure, cumulative exposure, fiber origin and characteristics (length and diameter), other possible confounding occupational or environmental exposures, and smoking. Methodological issues commonly presenting problems in evaluation of these data include assessment of the adequacy of environmental exposures, particularly in regard to fiber identification, distribution, and concentration over the duration of exposure, and the adequacy of study design to detect health effects (disease frequency, latency, and cohort size). Research priorities include further assessment and standardization of pleural thickening relative to fiber exposure, uniform mesothelioma surveillance, further epidemiological assessment of certain silicate and man-made mineral fiber cohorts with emphasis given to assessment of tremolite and small diameter glass and ceramic fibers. Further assessment of possible health risks of the general public should await improved definition of relevant fiber exposure in ambient air.

Topics: Asbestos; Asbestosis; Humans; Lung Neoplasms; Mesothelioma; Minerals; Neoplasms; Pleural Diseases; Respiratory Tract Diseases; Silicon

The article presents the influence of silicon carbide upon an organism, on the basis of the publications which, according to Chemical Abstracts, appeared on this subject from 1944 until 1987. The insolubility of silicon carbide, in the liquids of an organism and its indigestibility are indicated. A connection is presented between the size and shape of micrograins and the probability of tumor formation in rats; and the difference between silicon carbide and other dusts in the absorption of x-rays, inhibition of the TTC-dehydrogenase activity, collagenisation of lesions, carcinogenicity are also presented. The problem of interpretation of radiological images of lungs in people exposed to the influence of carborundum dust is dealt with. The biological inertness of silicon carbide is questioned.

Topics: Animals; Carbon; Carbon Compounds, Inorganic; Humans; Lung Diseases; Neoplasms; Neoplasms, Experimental; Occupational Diseases; Silicon; Silicon Compounds

Topics: Humans; N-Acetylneuraminic Acid; Neoplasms; Photochemotherapy; Photothermal Therapy; Quantum Dots; Reactive Oxygen Species; Silicon

As an emerging treatment method, photodynamic therapy (PDT) has attracted considerable interest due to the characteristics of non-invasiveness, repeatable treatment, high spatiotemporal resolution and few side effects. However, the life span (<40 ns) and diffusion distance (<20 nm) of reactive oxygen species such as singlet oxygen (

Topics: Humans; Lysosomes; Neoplasms; Photochemotherapy; Photosensitizing Agents; Precision Medicine; Quantum Dots; Silicon

The concept of using two-photon excitation in the NIR for the spatiotemporal control of biological processes holds great promise. However, its use for the delivery of nucleic acids has been very scarcely described and the reported procedures are not optimal as they often involve potentially toxic materials and irradiation conditions. This work prepares a simple system made of biocompatible porous silicon nanoparticles (pSiNP) for the safe siRNA photocontrolled delivery and gene silencing in cells upon two-photon excitation. PSiNP are linked to an azobenzene moiety, which possesses a lysine group (pSiNP@ICPES-azo@Lys) to efficiently complex siRNA. Non-linear excitation of the two-photon absorber system (pSiNP) followed by intermolecular energy transfer (FRET) to trans azobenzene moiety, result in the photoisomerization of the azobenzene from trans to cis and in the destabilization of the azobenzene-siRNA complex, thus inducing the delivery of the cargo siRNA to the cytoplasm of cells. Efficient silencing in MCF-7 expressing stable firefly luciferase with siRNAluc against luciferase is observed. Furthermore, siRNA against inhibitory apoptotic protein (IAP) leads to over 70% of MCF-7 cancer cell death. The developed technique using two-photon light allows a unique high spatiotemporally controlled and safe siRNA delivery in cells in few seconds of irradiation.

Topics: Cell Line, Tumor; Humans; Nanoparticles; Neoplasms; Porosity; RNA, Small Interfering; Silicon; Transfection

Porous silicon nanoparticles (pSiNPs) are widely utilized as drug carriers due to their excellent biocompatibility, large surface area, and versatile surface chemistry. However, the dispersion in pore size and biodegradability of pSiNPs arguably have hindered the application of pSiNPs for controlled drug release. Here, a step-changing solution to this problem is described involving the design, synthesis, and application of three different linker-drug conjugates comprising anticancer drug doxorubicin (DOX) and different stimulus-cleavable linkers (SCLs) including the photocleavable linker (ortho-nitrobenzyl), pH-cleavable linker (hydrazone), and enzyme-cleavable linker (β-glucuronide). These SCL-DOX conjugates are covalently attached to the surface of pSiNP via copper (I)-catalyzed alkyne-azide cycloaddition (CuAAC, i.e., click reaction) to afford pSiNP-SCL-DOXs. The mass loading of the covalent conjugation approach for pSiNP-SCL-DOX reaches over 250 µg of DOX per mg of pSiNPs, which is notably twice the mass loading achieved by noncovalent loading. Moreover, the covalent conjugation between SCL-DOX and pSiNPs endows the pSiNPs with excellent stability and highly controlled release behavior. When tested in both in vitro and in vivo tumor models, the pSiNP-SCL-DOXs induces excellent tumor growth inhibition.

Topics: Doxorubicin; Drug Carriers; Humans; Nanoparticles; Neoplasms; Porosity; Silicon

Fluorescent silicon nanodots have shown great prospects for bioimaging and biosensing applications. Although various fluorescent silicon-containing nanodots (SiNDs) have been developed, there are few reports about renal-clearable multicolor SiNDs. Herein, renal-clearable multicolor fluorescent SiNDs are synthesized by using silane molecules and organic dyes through a facile one-step hydrothermal method. The fluorescence of the resulting SiNDs can be tuned to blue (bSiNDs), green (gSiNDs), and red (rSiNDs) by simply changing the categories of silane reagents or dye molecules. The as-prepared SiNDs exhibit strong fluorescence with a quantum yield up to 72%, excellent photostability, and good biocompatibility with 12 h renal clearance rate as high as 86% ID. These properties enabled the SiNDs for tumor fluorescence imaging and H

Topics: Coloring Agents; Fluorescent Dyes; Humans; Hydrogen Peroxide; Neoplasms; Optical Imaging; Quantum Dots; Silanes; Silicon

Photothermal therapy (PTT) in combination with other treatment modalities has shown great potential to activate immunotherapy against tumor metastasis. However, the nanoparticles (NPs) that generate PTT have served as the photothermal agent only. Moreover, researchers have widely utilized highly immunogenic tumor models to evaluate the immune response of these NPs thus giving over-optimistic results. In the present study black porous silicon (BPSi) NPs were developed to serve as both the photothermal agent and the adjuvant for PTT-based antitumor immunotherapy. We found that the poorly immunogenic tumor models such as B16 are more valid to evaluate NP-based immunotherapy than the widely used immunogenic models such as CT26. Based on the B16 cancer model, a cocktail regimen was developed that combined BPSi-based PTT with doxorubicin (DOX) and cytosine-phosphate-guanosine (CpG). BPSi-based PTT was an important trigger to activate the specific immunotherapy to inhibit tumor growth by featuring the selective upregulation of TNF-α. Either by adding a low dose DOX or by prolonging the laser heating time, a similar efficacy of immunotherapy was evoked to inhibit tumor growth. Moreover, BPSi acted as a co-adjuvant for CpG to significantly boost the immunotherapy. The present study demonstrates that the BPSi-based regimen is a potent and safe antitumor immunotherapy modality. Moreover, our study highlighted that tuning the laser heating parameters of PTT is an alternative to the toxic cytostatic to evoke immunotherapy, paving the way to optimize the PTT-based combination therapy for enhanced efficacy and decreased side effects. STATEMENT OF SIGNIFICANCE: Tumor metastasis causes directly or indirectly more than 90% of cancer deaths. Combination of photothermal therapy (PTT), chemotherapy and immunotherapy based on nanoparticles (NPs) has shown great potential to inhibit distant and metastatic tumors. However, these NPs typically act only as photothermal agents and many of them have been evaluated with immunogenic tumor models. The present study developed black porous silicon working as both the photothermal conversion agent and the immunoadjuvant to inhibit distant tumor. It was recognized that the poorly immunogenic tumor model B16 is more appropriate to evaluate immunotherapy than the widely used immunogenic model CT26. The coordination mechanism of the PTT-based combination therapy regimen was discovered in detail, paving the way to optimize cancer immunotherapy

Topics: Adjuvants, Immunologic; Cell Line, Tumor; Cytosine; Cytostatic Agents; Doxorubicin; Guanosine; Humans; Hyperthermia, Induced; Immunotherapy; Nanoparticles; Neoplasms; Phosphates; Phototherapy; Porosity; Silicon; Tumor Necrosis Factor-alpha

Topics: Animals; Cell Line, Tumor; Ligands; Mice; Nanoparticles; Neoplasms; Peptide Hydrolases; Peptides; Porosity; Silicon

An approach to differentially modify the internal surface of porous silicon nanoparticles (pSiNPs) with hydrophobic dodecene and the external surface with antifouling poly-

Topics: Antineoplastic Agents; Cell Line, Tumor; Drug Delivery Systems; Humans; Nanoparticles; Neoplasms; Porosity; Silicon

Silicon, a highly biocompatible and ubiquitous chemical element in living systems, exhibits great potentials in biomedical applications. However, the silicon-based nanomaterials such as silica and porous silicon have been largely limited to only serving as carriers for delivery systems, due to the lack of intrinsic functionalities of silicon. This work presents the facile construction of a two-dimensional (2D) hydrogen-bonded silicene (H-silicene) nanosystem which is highlighted with tunable bandgap and selective degradability for tumor-specific photodynamic therapy facilely by surface covalent modification of hydrogen atoms. Briefly, the H-silicene nanosheet material is selectively degradable in normal neutral tissues but rather stable in the mildly acidic tumor microenvironment (TME) for achieving efficient photodynamic therapy (PDT). Such a 2D hydrogen-bonded silicene nanosystem featuring the tunable bandgap and tumor-selective degradability provides a new paradigm for the application of multi-functional two-dimensional silicon-based biomaterials towards the diagnosis and treatments of cancer and other diseases.

Topics: Humans; Hydrogen; Neoplasms; Photochemotherapy; Silicon; Tumor Microenvironment

Macrophage cell membrane-camouflaged nanocarriers can effectively reduce immune cell clearance and actively target tumors. In this study, a macrophage cell membrane-camouflaged mesoporous silica nanorod (MSNR)-based antitumor drug carrier equipped with a cationic polymer layer was developed. As drug carriers, these MSNRs were loaded with the thermosensitive phase change material L-menthol (LM), the chemotherapy drug doxorubicin (DOX) and the fluorescent molecule indocyanine green (ICG). The rod-like shape of the MSNRs was shown to enhance the penetration of the drug carriers to tumors. In the weakly acidic tumor microenvironment, the cationic polymer exhibited a proton sponge effect to trigger macrophage cell membrane coating detachment, promoting tumor cell uptake. Following nanocarrier uptake, ICG is heated by near-infrared (NIR) irradiation to make LM undergo a phase transition to release DOX and generate a synergistic effect of thermochemotherapy which kills tumor cells and inhibits tumor growth together with reactive oxygen species (ROS) produced by ICG. Overall, this nanohybrid drug delivery system demonstrates an intelligent cascade response, leads to tissue-cell specific targeting and improves drug release accuracy, thus proving to be an effective cancer therapy.

Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Membrane; Cell Survival; Doxorubicin; Drug Delivery Systems; Humans; Indocyanine Green; Infrared Rays; Macrophages; Nanotubes; Neoplasms; Photochemotherapy; Photothermal Therapy; Silicon

Early and accurate detection of breast cancer plays an important role in improving the survival rates of patients. In this work, we designed and synthesized the Gal-NAc-imprinted nanoparticles (GIPs) via boronate-affinity glycan-oriented surface imprinting strategy. Molecularly imprinted polymers (MIPs) were hybridized with fluorescent silicon nanoparticles (SiNPs) to target Tn antigens. However, the single fluorescent imaging mode is not conducive to obtaining accurate diagnosis, due to its poor tissue penetration. To resolve this obstacle, doping gadolinium (Gd) into SiNPs was adopted to emerge an extra significant magnetic resonance (MR) signal, achieving highly sensitive fluorescence imaging and magnetic resonance imaging (MRI) with high spatial resolution. GIPs had uniform particle size around 31.8 nm, and exhibited satisfactory fluorescence stability. The maximum adsorption capacity of GIPs was 1.15 μM/g with a high imprinting factor (IF) of 7.5. Confocal laser scanning microscope imaging revealed that the GIPs had excellent specific recognition ability with a low cytotoxicity. GIPs also showed an outstanding MR performance on cancer cells. Therefore, the synthesized nanoparticles had desirable performance in dual-model imaging to specifically target recognition cancer cells. It may have a tremendous potential in real biological samples.

Topics: Gadolinium; Humans; Molecular Imprinting; Nanoparticles; Neoplasms; Polymers; Polysaccharides; Silicon

A novel amine-functionalized silica quantum dots (SiQDs) fluorescent nanoprobe was developed for sensing of lead concentration in water, plasma and cell lysate. In addition, the developed probe was utilized for bioimaging of intracellular lead ions in HT 29 cancer cells. The amine-functionalized nanoprobe exhibited fluorescence emission at 445 nm under excitation at 355 nm. Upon addition of lead ions, the fluorescence of SiQDs linearly enhanced from 50 ng/mL to 5 µg/mL and 50 ng/mL to 25 µg/mL for plasma and standard media, respectively. The synthesis and fabrication of this probe are simple and serves high sensitivity with a limit of detection down to around 20 ng/mL. In the presence of various molecular and ion interfering, reliable results are obtained, confirming the specificity of the nanoprobe for lead ion detection. Meanwhile, amine-functionalized SiQD-based nanoprobe exhibits excellent cell membrane-permeability and biocompatibility. Thus, this probe is utilized for lead tracing in HT 29 cancer live cells. Fluorescent microscopy results confirmed the attachment of the produced nanomaterials to the HT 29 cancer cells.

Topics: Amines; Fluorescent Dyes; Ions; Lead; Neoplasms; Quantum Dots; Silicon

In vitro, the nanoplatform catalyzed NO's release with the maximum value of 4.91 μM within 60 min at 43°C pH=5.0, which was increased by 1.14 times when the temperature was 37°C. In vivo, 11.7 μg Au in the tumor tissue was found to catalyze S-nitrosoglutathione continuously, and 54 μM NO was checked out in the urine.. The high concentration of NO was found to increase the apoptotic rate and to reduce tumor proliferation. In the chemo-photothermal combination therapy, the tumor inhibition rate was increased up to 94.3%, and Au's contribution from catalyzing NO release NO was 8.17%.

Topics: Catalysis; Cell Death; Cell Proliferation; Doxorubicin; Drug Liberation; Endocytosis; Folic Acid; Gold; Humans; Magnetic Phenomena; MCF-7 Cells; Nanoparticles; Neoplasms; Nitric Oxide; Particle Size; Photothermal Therapy; Porosity; Silicon; X-Ray Diffraction

One of the recent advances in nanotechnology within the medical field is the development of a nanoformulation of anticancer drugs or photosensitizers. Cancer cell-specific drug delivery and upregulation of the endogenous level of reactive oxygen species (ROS) are important in precision anticancer treatment. Within our article, we report a new therapeutic nanoformulation of cancer cell targeting using endogenous ROS self-generation without an external initiator and a switch-on drug release (ROS-induced cascade nanoparticle degradation and anticancer drug generation). We found a substantial cellular ROS generation by treating an isothiocyanate-containing chemical and functionalizing it onto the surface of porous silicon nanoparticles (pSiNPs) that are biodegradable and ROS-responsive nanocarriers. Simultaneously, we loaded an ROS-responsive prodrug (JS-11) that could be converted to the original anticancer drug, SN-38, and conducted further surface functionalization with a cancer-targeting peptide, CGKRK. We demonstrated the feasibility as a cancer-targeting and self-activating therapeutic nanoparticle in a pancreatic cancer xenograft mouse model, and it showed a superior therapeutic efficacy through ROS-induced therapy and drug-induced cell death. The work presented is a new concept of a nanotherapeutic and provides a more feasible clinical translational pathway.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Drug Liberation; Female; Humans; Irinotecan; Isothiocyanates; Male; Mice, Inbred BALB C; Mice, Nude; Nanoparticles; Neoplasms; Oligopeptides; Photosensitizing Agents; Precision Medicine; Prodrugs; Reactive Oxygen Species; Silanes; Silicon; Xenograft Model Antitumor Assays

Topics: Animals; Carbocyanines; Cell Line, Tumor; Female; Fluorescent Dyes; Liver; Mice; Mice, Inbred BALB C; Nanoparticles; Neoplasms; Optical Imaging; Particle Size; Polyethylene Glycols; Porosity; RAW 264.7 Cells; Silicon; Spleen; Tissue Distribution

Silicon and metallic are two types of stents in use. In this study, we compared complications and long-term survival among patients who received silicon or fully covered, bifurcated self-expandable metallic stents (SEMS) for a malignant tracheobronchial obstruction and/or tracheo/bronchial oesophageal fistulas.. Patients in whom Y-shaped stents were used from January 2013 to June 2017 in our interventional pulmonology unit were evaluated retrospectively from patient files.. Of the 47 patients, 30 (23 males, 76.7%) were in the silicon stent group and 17 (14 males, 82.4%) were in the covered SEMS group. No differences between the groups were detected in ECOG status, pathological properties of the disease, radiotherapy or chemotherapy history before the procedure, symptoms at presentation, or comorbidities. The most common symptom was dyspnoea (96.7% and 100%), and the most common comorbidity was chronic obstructive pulmonary disease (26.7% and 23.5%). A total of 20 complications (42.6%) were seen, with no significant difference between the groups (silicon, 40%; SEMS, 47.1%; P = . 62). Mean survival was 164.51 ± 38.83 days for the silicon stent group and 254.45 ± 103.32 days for the SEMS group (P = .588). No differences were observed in 30-, 90- or 180-day mortality between the two groups (P = .966, .846 and .534, respectively).. No significant differences in symptom palliation, insertion safety, complication rate or survival were detected between the two types of stent.

Topics: Airway Obstruction; Bronchial Fistula; Bronchoscopy; Case-Control Studies; Comorbidity; Dyspnea; Female; Humans; Male; Neoplasms; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Safety; Self Expandable Metallic Stents; Silicon; Stents; Survival Analysis; Treatment Outcome

The purpose of study is to investigate the dosimetry of electron intraoperative radiotherapy (IOERT) of the Intraop Mobetron 2000 mobile LINAC in treatments outside of the breast. After commissioning and external validation of dosimetry, we report in vivo results of measurements for treatments outside the breast in a large patient cohort, and investigate if the presence of inhomogeneities can affect in vivo measurements.. Applicator factors and profile curves were measured with a stereotactic diode. The applicators factors of the 6 cm flat and beveled applicators were also confirmed with radiochromic films, parallel-plate ion chamber and by an external audit performed with ThermoLuminescent Dosimeters (TLDs). The influence of bone on dose was investigated by using radiochromic films attached to an insert equivalent to cortical bone, immersed in the water phantom. In vivo dosimetry was performed on 126 patients treated with IOERT using metal oxide-silicon semiconductor field effect transistors (MOSFETs) placed on the tumor bed.. Relatively small differences were found among different detectors for measurements of applicator factors. In the external audit, the agreement with the TLD was mostly within ±0.2%. The largest increase of dose due to the presence of cortical bone insert was +6.0% with energy 12 MeV and 3 cm applicator. On average, in vivo dose was significantly (+3.1%) larger than prescribed dose.. IOERT in applications outside the breast results in low discrepancies between in vivo and prescribed doses, which can be also explained with the presence of tissue inhomogeneity.

Topics: Bone and Bones; Breast; Electrons; Female; Film Dosimetry; Humans; Intraoperative Period; Male; Neoplasms; Particle Accelerators; Phantoms, Imaging; Radiometry; Radiotherapy; Reproducibility of Results; Semiconductors; Silicon; Thermoluminescent Dosimetry

Currently, the nanocomposites based on silicon nanoparticles (SiNPs) are usually limited to a single therapeutic modality, and the design of the SiNPs nanohybrids with multi-modal synergistic therapeutic functions is still worth being explored to achieve more effective treatment. Herein, we used mesoporous silica nanoparticle (MSN) as a nanoplatform, SiNPs and the photosensitizer 5,10,15,20-tetrakis (1-methyl 4-pyridinio) porphyrin tetra (p-toluenesulfonate) (TMPyP) were first embedded in the MSN and was further modified with folic acid (FA) to obtain the mesoporous silica nanocomposite (MSN@SiNPs@TMPyP-FA) for targeted two-photon-excited fluorescence imaging-guided photodynamic therapy (PDT) and chemotherapy. The embedded TMPyP could generate singlet oxygen to perform PDT under light irradiation, meanwhile the anticancer drugs doxorubicin (DOX) could be loaded for chemotherapy. Moreover, due to the two-photon excited fluorescence of SiNPs, the nanocomposite successfully achieved targeted two-photon fluorescence cellular imaging at the near-infrared (NIR) laser excitation, which could effectively avoid the interference of biological auto-fluorescence. And in vitro cytotoxicity assays revealed that the synergistic therapy combining PDT and chemotherapy exhibited high therapeutic efficacy for cancer cells.

Topics: A549 Cells; Antineoplastic Agents; Doxorubicin; Drug Delivery Systems; Humans; MCF-7 Cells; Nanoparticles; Neoplasms; Optical Imaging; Photochemotherapy; Photosensitizing Agents; Porphyrins; Silicon; Silicon Dioxide; Theranostic Nanomedicine

Lactate, the main contributor to the acidic tumor microenvironment, not only promotes the proliferation of tumor cells, but also closely relates to tumor invasion and metastasis. Here, a tumor targeting nanoplatform, designated as Me&Flu@MSN@MnO

Topics: Antineoplastic Agents; Cell Line, Tumor; Fluvastatin; Folic Acid; Humans; Lactates; Manganese Compounds; Metformin; Nanoparticles; Neoplasm Metastasis; Neoplasms; Porosity; Silicon; Tumor Microenvironment

Luminescent probes based on silicon nanocrystals (SiNCs) have many advantages for bioimaging compared to more conventional quantum dots: abundancy of silicon combined with its biocompatibility; tunability of the emission color of SiNCs in the red and NIR spectral region to gain deeper tissue penetration; long emission lifetimes of SiNCs (hundreds of μs) enabling time-gated acquisitions to avoid background noise caused by tissue autofluorescence and scattered excitation light. Here we report a new three-step synthesis, based on a low temperature thiol-ene click reaction that can afford SiNCs, colloidally stable in water, with preserved bright red and NIR photoluminescence (band maxima at 735 and 945 nm for nanocrystals with diameters of 4 and 5 nm, respectively) and long emission lifetimes. Their luminescence is insensitive to dioxygen and sensitive to pH changes in the physiological range, enabling pH sensing. In vivo studies demonstrated tumor accumulation, 48 hours clearance and a 3-fold improvement of the signal-to-noise ratio compared to steady-state imaging.

Topics: Animals; Cell Line, Tumor; Click Chemistry; Fluorescent Dyes; Humans; Hydrogen-Ion Concentration; Mice; Mice, Nude; Nanoparticles; Neoplasms; Polyethylene Glycols; Signal-To-Noise Ratio; Silicon; Spectroscopy, Near-Infrared; Tissue Distribution; Water; Xenograft Model Antitumor Assays

Developing biomimetic nanoparticles without loss of the integrity of proteins remains a major challenge in cancer chemotherapy. Here, we develop a biocompatible tumor-cell-exocytosed exosome-biomimetic porous silicon nanoparticles (PSiNPs) as drug carrier for targeted cancer chemotherapy. Exosome-sheathed doxorubicin-loaded PSiNPs (DOX@E-PSiNPs), generated by exocytosis of the endocytosed DOX-loaded PSiNPs from tumor cells, exhibit enhanced tumor accumulation, extravasation from blood vessels and penetration into deep tumor parenchyma following intravenous administration. In addition, DOX@E-PSiNPs, regardless of their origin, possess significant cellular uptake and cytotoxicity in both bulk cancer cells and cancer stem cells (CSCs). These properties endow DOX@E-PSiNPs with great in vivo enrichment in total tumor cells and side population cells with features of CSCs, resulting in anticancer activity and CSCs reduction in subcutaneous, orthotopic and metastatic tumor models. These results provide a proof-of-concept for the use of exosome-biomimetic nanoparticles exocytosed from tumor cells as a promising drug carrier for efficient cancer chemotherapy.

Topics: Animals; Cell Line, Tumor; Disease Models, Animal; Doxorubicin; Drug Carriers; Drug Compounding; Exocytosis; Exosomes; Female; Humans; Male; Mice; Nanoparticles; Neoplasms; Neoplastic Stem Cells; Porosity; Proof of Concept Study; Silicon; Spheroids, Cellular; Xenograft Model Antitumor Assays

Silicon nanoparticles (SiNPs), especially those emitting red fluorescence, have been widely applied in the field of bioimaging. However, harsh synthetic conditions and strong biological autofluorescence caused by short wavelength excitation restrict the further development of SiNPs in the field of biological applications. Here, we report a method for synthesizing a ruthenium-complex-functionalized two-photon-excited red fluorescence silicon nanoparticle composite (SiNPs-Ru) based on fluorescence resonance energy transfer under mild experimental conditions. In the prepared SiNPs-Ru composite, silicon nanoparticles synthesized by atmospheric pressure microwave-assisted synthesis served as a fluorescence energy donor, which had two-photon fluorescence properties, and tris(4,4'-dicarboxylic acid-2,2-bipyridyl)ruthenium(II) dichloride (L

Topics: Animals; Cell Survival; Coordination Complexes; Fluorescence Resonance Energy Transfer; Fluorescent Dyes; Folic Acid; HeLa Cells; Humans; Mice; Mice, Nude; Microwaves; Nanoparticles; Neoplasms; Optical Imaging; Photochemotherapy; Ruthenium; Silicon; Singlet Oxygen; Toxicity Tests; Zebrafish

Silicon-based biomaterials play an indispensable role in biomedical engineering; however, due to the lack of intrinsic functionalities of silicon, the applications of silicon-based nanomaterials are largely limited to only serving as carriers for drug delivery systems. Meanwhile, the intrinsically poor biodegradation nature for silicon-based biomaterials as typical inorganic materials also impedes their further in vivo biomedical use and clinical translation. Herein, by the rational design and wet chemical exfoliation synthesis of the 2D silicene nanosheets, traditional 0D nanoparticulate nanosystems are transformed into 2D material systems, silicene nanosheets (SNSs), which feature an intriguing physiochemical nature for photo-triggered therapeutics and diagnostic imaging and greatly favorable biological effects of biocompatibility and biodegradation. In combination with DFT-based molecular dynamics (MD) calculations, the underlying mechanism of silicene interactions with bio-milieu and its degradation behavior are probed under specific simulated physiological conditions. This work introduces a new form of silicon-based biomaterials with 2D structure featuring biodegradability, biocompatibility, and multifunctionality for theranostic nanomedicine, which is expected to promise high clinical potentials.

Topics: Density Functional Theory; Models, Molecular; Molecular Conformation; Neoplasms; Silicon; Theranostic Nanomedicine

We designed and synthesized an activatable near-infrared (NIR) fluorescent probe for γ-glutamyltransferase, based on an asymmetric silicon rhodamine scaffold with an optimized equilibrium of intramolecular spirocyclization. The synthesized probe exhibits dramatic NIR fluorescence activation and, in combination with previously reported probes, enables discrimination of tumors with different enzymatic profiles.

Topics: Animals; Cell Line, Tumor; Fluorescent Dyes; gamma-Glutamyltransferase; Humans; Mice; Microscopy, Confocal; Neoplasms; Optical Imaging; Rhodamines; Silicon

Monitoring the pH dependent behavior of normal and cancer cells by impedimetric biosensor based on Silicon Nanowires (SiNWs) was introduced to diagnose the invasive cancer cells. Autophagy as a biologically activated process in invasive cancer cells during acidosis, protect them from apoptosis in lower pH which presented in our work. As the autophagy is the only activated pathways which can maintain cellular proliferation in acidic media, responses of SiNW-ECIS in acidified cells could be correlated to the probability of autophagy activation in normal or cancer cells. In contrast, cell survival pathway wasn't activated in low-grade cancer cells which resulted in their acidosis. The measured electrical resistance of MCF10, MCF7, and MDA-MB468 cell lines, by SiNW sensor, in normal and acidic media were matched by the biological analyses of their vital functions. Invasive cancer cells exhibited increased electrical resistance in pH 6.5 meanwhile the two other types of the breast cells exhibited sharp (MCF10) and moderate (MCF7) decrease in their resistance. This procedure would be a new trend in microenvironment based cancer investigation.

Topics: Apoptosis; Autophagy; Biosensing Techniques; Cell Proliferation; Cell Survival; Electric Impedance; Humans; Hydrogen-Ion Concentration; MCF-7 Cells; Nanowires; Neoplasms; Silicon

Tumor pH detection and pH value change monitoring have been of great interest in the field of nanomedicine. In this study, a pH-sensitive near-infrared fluorescence probe SiRB (Si-rhodamine and Boronic acid group) was synthesized by introducing a boronic acid group into the silicon rhodamine structure. ICG (Indocyanine green) as the fluorescence internal standard and SiRB were loaded into PLGA (poly lactic-co-glycolic acid) to form PLGA-SiRB-ICG nanoparticle. The experiments showed that the size of the nanoparticle was about 90 nm, which can reach tumor passively by enhancing permeability and retention effect. PLGA in the acidic environment will accelerate the release of cleavage, and the fluorescence ratio of the two probes can reflect the specific pH value in the tumor. The results indicated that the nanoparticle could quantitatively measure the pH value of the tumor site, which is expected to be used in tumor research and treatment.

Topics: Animals; Boronic Acids; Cell Survival; Fluorescence; Fluorescent Dyes; Humans; Hydrogen-Ion Concentration; Indocyanine Green; Lactic Acid; MCF-7 Cells; Mice; Microscopy, Confocal; Nanoparticles; Neoplasms; Optical Imaging; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Rhodamines; Silicon

This paper presents the feasibility study of a novel 3D mesa bridge microdosimeter and its use for BNCT dosimetry. The performance of the microdosimeter was studied using Monte Carlo simulation. The clinical BNCT field at Kyoto University Reactor (KUR) using both thermal and epithermal irradiation modes were used in this study. Results show that this microdosimeter can be utilised as an effective tool to measure microdosimetric spectrum in the BNCT field and experimental validation will follow once KUR is operational.

Topics: Alpha Particles; Boron Neutron Capture Therapy; Computer Simulation; Feasibility Studies; Humans; Lithium; Monte Carlo Method; Neoplasms; Phantoms, Imaging; Radiometry; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Silicon

Self-controlled hyperthermia is a non-invasive technique used to kill or destroy cancer cells while preserving normal surrounding tissues. We have explored bulk magnetic Ni-Si and Ni-Al alloys as a potential thermoseeds. The structural, magnetic and magnetocaloric properties of the samples were investigated, including saturation magnetisation, Curie temperature (T

Topics: Alloys; Aluminum; Hot Temperature; Hyperthermia, Induced; Magnetic Phenomena; Neoplasms; Nickel; Silicon

There is a pressing need to develop more effective therapeutics to fight cancer. An idyllic chemotherapeutic is expected to overcome drug resistance of tumors and minimize harmful side effects to healthy tissues. Antibody-functionalized porous silicon nanoparticles loaded with a combination of chemotherapy drug and gold nanoclusters (AuNCs) are developed. These nanocarriers are observed to selectively deliver both payloads, the chemotherapy drug and AuNCs, to human B cells. The accumulation of AuNCs to target cells and subsequent exposure to an external electromagnetic field in the microwave region render them more susceptible to the codelivered drug. This approach represents a targeted two-stage delivery nanocarrier that benefits from a dual therapeutic action that results in enhanced cytotoxicity.

Topics: Drug Delivery Systems; Gold; Nanoparticles; Neoplasms; Porosity; Silicon

Circulating tumor cells (CTCs) have been implicated as the seeds of cancer metastasis and therefore have the potential to provide significant prognostic and diagnostic values. Here, we describe a procedure for separating CTCs from whole blood based on size and deformability using the microfluidic ratchet device. This device leverages the ratcheting motion of single cells created as they are deformed through funnel-shaped constrictions using oscillatory flow in order to divert cells based on differences in size and deformability. Subsequent methods for CTC identification and enumeration using immunofluorescence after separation are also described.

Topics: Biomechanical Phenomena; Cell Count; Cell Separation; Cell Size; Fluorescent Antibody Technique; Humans; Microfluidic Analytical Techniques; Neoplasms; Neoplastic Cells, Circulating; Rheology; Silicon

Immunoadjuvant porous silicon (PSi)-based nanovaccines are prepared by nanoprecipitation in a glass capillary microfluidics device. Vesicles, derived from cancer cell membranes encapsulating thermally oxidized PSi nanoparticles or PSi-polymer nanosystems binding a model antigen, are biocompatible over a wide range of concentrations, and show immunostimulant properties in human cells, promoting the expression of co-stimulatory signals and the secretion of pro-inflammatory cytokines.

Topics: Cell Membrane; Dextrans; Humans; Immunotherapy; Neoplasms; Porosity; Silicon

To develop photothermal and biodegradable nanocarriers for combined chemo-photothermal therapy of cancer, polyaniline/porous silicon hybrid nanocomposites had been successfully fabricated via surface initiated polymerization of aniline onto porous silicon nanoparticles in our experiments. As-prepared polyaniline/porous silicon nanocomposites could be well dispersed in aqueous solution without any extra hydrophilic surface coatings, and showed a robust photothermal effect under near-infrared (NIR) laser irradiation. Especially, after an intravenous injection into mice, these biodegradable porous silicon-based nanocomposites as non-toxic agents could be completely cleared in body. Moreover, these polyaniline/porous silicon nanocomposites as drug carriers also exhibited an efficient loading and dual pH/NIR light-triggered release of doxorubicin hydrochloride (DOX, a model anticancer drug). Most importantly, assisted with NIR laser irradiation, polyaniline/PSiNPs nanocomposites with loading DOX showed a remarkable synergistic anticancer effect combining chemotherapy with photothermal therapy, whether in vitro or in vivo. Therefore, based on biodegradable PSiNPs-based nanocomposites, this combination approach of chemo-photothermal therapy would have enormous potential on clinical cancer treatments in the future.. Considering the non-biodegradable nature and potential long-term toxicity concerns of photothermal nanoagents, it is of great interest and importance to develop biodegradable and photothermal nanoparticles with an excellent biocompatibility for their future clinical applications. In our experiments, we fabricated porous silicon-based hybrid nanocomposites via surface initiated polymerization of aniline, which showed an excellent photothermal effect, aqueous dispersibility, biodegradability and biocompatibility. Furthermore, after an efficient loading of DOX molecules, polyaniline/porous silicon nanocomposites exhibited the remarkable synergistic anticancer effect, whether in vitro and in vivo.

Topics: Aniline Compounds; Animals; Biocompatible Materials; Cell Death; Cell Line, Tumor; Doxorubicin; Drug Carriers; Drug Liberation; Human Umbilical Vein Endothelial Cells; Hydrogen-Ion Concentration; Hyperthermia, Induced; Light; Mice, Inbred BALB C; Nanocomposites; Neoplasms; Phototherapy; Porosity; Silicon; Spectrophotometry, Ultraviolet; Spectroscopy, Near-Infrared

Silicon nanoparticles (SiNPs) prepared by mechanical grinding of luminescent porous silicon were coated with a biopolymer (dextran) and investigated as a potential theranostic agent for bioimaging and sonodynamic therapy. Transmission electron microscopy, photoluminescence and Raman scattering measurements of dextran-coated SiNPs gave evidence of their enhanced stability in water. In vitro experiments confirmed the lower cytotoxicity of the dextran-coated NPs in comparison with uncoated ones, especially for high concentrations of about 2 mg ml

Topics: 3T3-L1 Cells; Animals; Cell Death; Cell Line, Tumor; Cell Survival; Coated Materials, Biocompatible; Dextrans; Dogs; Humans; Luminescence; Mice; Nanoparticles; Neoplasms; Silicon; Spectrum Analysis, Raman; Theranostic Nanomedicine; Time Factors; Ultrasonic Waves

Combining the merits of delivery vectors with drug molecules is one of the key directions for development of efficient cancer monitoring and treatment techniques. In this work, a novel type of silicon based composite nanoparticles (NPs) with incorporated hydrophobic phthalocyanine molecules (Pc) was synthesized via a facile one-pot method. The as-synthesized Pc@Si NPs, with a small size of 4.2 ± 0.8 nm, have excellent dispersibility in water and good biocompatibility with cells, in addition to favorable photoluminescence and robust photostability even in cells. Moreover, the Pc@Si NPs show significant in vitro cancer cell killing and in vivo tumor inhibiting abilities upon near-infrared light exposure, due to the photodynamic therapy (PDT) effect of Pc. This work develops an efficient fluorescent PDT drug carrier; moreover, the facile one-pot synthesis strategy may be used generally to prepare silicon-based composite NPs incorporated with diverse hydrophobic drugs/diagnostic molecules for a wide range of biomedical applications.

Topics: Cell Line, Tumor; Cell Survival; Diagnostic Imaging; Endocytosis; Fluorescence; Humans; Indoles; Isoindoles; Nanoparticles; Neoplasms; Photochemotherapy; Quantum Dots; Silicon

The main objective of this study is to demonstrate the performance characteristics of the Magic Plate (MP) system when operated upstream of the patient in trans-mission mode (MPTM). The MPTM is an essential component of a real-time QA system designed for operation during radiotherapy treatment. Of particular interest is a quantitative study into the influence of the MP on the radiation beam quality at several field sizes and linear accelerator potential differences. The impact is measured through beam perturbation effects such as changes in the skin dose and/or percentage depth dose (PDD) (both in and out of field). The MP was placed in the block tray of a Varian linac head operated at 6, 10 and 18 MV beam energy. To optimize the MPTM operational setup, two conditions were investigated and each setup was compared to the case where no MP is positioned in place (i.e., open field): (i) MPTM alone and (ii) MPTM with a thin passive contamination electron filter. The in-field and out-of-field surface doses of a solid water phantom were investigated for both setups using a Markus plane parallel (Model N23343) and Attix parallel-plate, MRI model 449 ionization chambers. In addition, the effect on the 2D dose distribution measured by the Delta4 QA system was also investi-gated. The transmission factor for both of these MPTM setups in the central axis was also investigated using a Farmer ionization chamber (Model 2571A) and an Attix ionization chamber. Measurements were performed for different irradiation field sizes of 5 × 5 cm2 and 10 × 10 cm2. The change in the surface dose relative to dmax was measured to be less than 0.5% for the 6 MV, 10 MV, and 18 MV energy beams. Transmission factors measured for both set ups (i & ii above) with 6 MV, 10 MV, and 18 MV at a depth of dmax and a depth of 10 cm were all within 1.6% of open field. The impact of both the bare MPTM and the MPTM with 1 mm buildup on 3D dose distribution in comparison to the open field investigated using the Delta4 system and both the MPTM versions passed standard clinical gamma analysis criteria. Two MPTM operational setups were studied and presented in this article. The results indicate that both versions may be suitable for the new real-time megavoltage photon treatment delivery QA system under development. However, the bare MPTM appears to be slightly better suited of the two MP versions, as it minimally perturbs the radiation field and does not lead to any significant increase in skin dose to t

Topics: Electrons; Humans; Magnetic Resonance Imaging; Neoplasms; Particle Accelerators; Phantoms, Imaging; Photons; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Image-Guided; Silicon; Water

Biodegradability of inorganic nanoparticles is one of the most critical issues in their further clinical translations. In this work, a novel "metal ion-doping" approach has been developed to endow inorganic mesoporous silica-based nanoparticles with tumor-sensitive biodegradation and theranostic functions, simply by topological transformation of mesoporous silica to metal-doped composite nanoformulations. "Manganese extraction" sensitive to tumor microenvironment was enabled in manganese-doped hollow mesoporous silica nanoparticles (designated as Mn-HMSNs) to fast promote the disintegration and biodegradation of Mn-HMSNs, further accelerating the breakage of Si-O-Si bonds within the framework. The fast biodegradation of Mn-HMSNs sensitive to mild acidic and reducing microenvironment of tumor resulted in much accelerated anticancer drug releasing and enhanced T1-weighted magnetic resonance imaging of tumor. A high tumor-inhibition effect was simultaneously achieved by anticancer drug delivery mediated by PEGylated Mn-HMSNs, and the high biocompatibility of composite nanosystems was systematically demonstrated in vivo. This is the first demonstration of biodegradable inorganic mesoporous nanosystems with specific biodegradation behavior sensitive to tumor microenvironment, which also provides a feasible approach to realize the on-demand biodegradation of inorganic nanomaterials simply by "metal ion-doping" strategy, paving the way to solve the critical low-biodegradation issue of inorganic drug carriers.

Topics: Animals; Antineoplastic Agents; Biocompatible Materials; Cell Survival; Doxorubicin; Drug Carriers; Drug Delivery Systems; Female; Hep G2 Cells; Humans; Magnetic Resonance Imaging; Manganese; Mice; Mice, Inbred BALB C; Mice, Nude; Microscopy, Electron, Transmission; Nanoparticles; Nanostructures; Neoplasms; Oxygen; Silicon; Silicon Dioxide; Theranostic Nanomedicine; Thermodynamics

Topics: Animals; Humans; Lasers; Nanoparticles; Neoplasms; Optical Imaging; Phototherapy; Silicon; Theranostic Nanomedicine

This paper describes the design and characterization of a charged particle imaging system composed of a position sensitive detector and residual range detector. The position detector consists of two identical overlying and orthogonal planes each of which consists of two layers of pre-aligned and juxtaposed scintillating fibres. The 500μm square section fibres are optically coupled to two Silicon Photomultiplier arrays using a channel reduction system patented by the Istituto Nazionale di Fisica Nucleare. The residual range detector consists of sixty parallel layers of the same fibres used in the position detector each of which is optically coupled to a Silicon Photomultiplier array by wavelength shifting fibres. The sensitive area of the two detectors is 9×9cm(2). Characterising the position sensitive and the residual range detectors to reconstruct the radiography, is fundamental to validating the detectors' designs. The proton radiography of a calibrated target in imaging conditions is presented. The spatial resolution of the position sensitive detector is about 150μm and the range resolution is about 170μm. The performance of the prototypes were tested at CATANA proton therapy facility (Laboratori Nazionali del Sud, INFN, Catania) with energy up to 58MeV and rate of about 10(6) particles per second. The comparison between the simulations and measurements confirms the validity of this system.

Topics: Calibration; Carbon; Computer Simulation; Equipment Design; Humans; Ions; Monte Carlo Method; Neoplasms; Optical Fibers; Proton Therapy; Protons; Radiography; Radiotherapy Planning, Computer-Assisted; Reproducibility of Results; Silicon; Water

We describe the current difference in reporting the performance of nanotechnology diagnostic devices between technologists and clinicians. This perspective specifies the "metrics" used to evaluate these devices and describes strategies to bridge the gap between these two communities in order to accelerate the translation from academic bench to the clinic. We use two recently published ACS Nano articles to highlight the evaluation of silicon nanowire and surface-enhanced Raman spectroscopy-breath diagnostic tests for patients afflicted with cancer and asthma. These studies represent some of the earliest studies of emerging nanotechnology devices utilizing clinical parameters to assess performance.

Topics: Humans; Nanomedicine; Nanotechnology; Nanowires; Neoplasms; Silicon; Spectrum Analysis, Raman

Drug delivery using synthetic nanoparticles including porous silicon has been extensively used to overcome the limitations of chemotherapy. However, their synthesis has many challenges such as lack of scalability, high cost, and the use of toxic materials with concerning environmental impact. Nanoscale materials obtained from natural resources are an attractive option to address some of these disadvantages. In this paper, a new mesoporous biodegradable silicon nanoparticle (SiNP) drug carrier obtained from natural diatom silica mineral available from the mining industry is presented. Diatom silica structures are mechanically fragmented and converted into SiNPs by simple and scalable magnesiothermic reduction process. Results show that SiNPs have many desirable properties including high surface area, high drug loading capacity, strong luminescence, biodegradability, and no cytotoxicity. The in-vitro release results from SiNPs loaded with anticancer drugs (doxorubicin) demonstrate a pH-dependent and sustained drug release with enhanced cytotoxicity against cancer cells. The cells study using doxorubicin loaded SiNPs shows a significantly enhanced cytotoxicity against cancer cells compared with free drug, suggesting their considerable potential as theranostic nanocarriers for chemotherapy. Their low-cost manufacturing using abundant natural materials and outstanding chemotherapeutic performance has made them as a promising alternative to synthetic nanoparticles for drug delivery applications.

Topics: Animals; Antineoplastic Agents; Cell Line; Cell Line, Tumor; Cell Survival; Delayed-Action Preparations; Diatoms; Doxorubicin; Drug Carriers; Drug Delivery Systems; Hydrogen-Ion Concentration; Luminescence; Macrophages; Mice; Nanoparticles; Neoplasms; RAW 264.7 Cells; Silicon; Silicon Dioxide; Theranostic Nanomedicine

New approaches for visualisation of silicon nanoparticles (SiNPs) in cancer cells are realised by means of the linear and nonlinear optics in vitro. Aqueous colloidal solutions of SiNPs with sizes of about 10-40 nm obtained by ultrasound grinding of silicon nanowires were introduced into breast cancer cells (MCF-7 cell line). Further, the time-varying nanoparticles enclosed in cell structures were visualised by high-resolution structured illumination microscopy (HR-SIM) and micro-Raman spectroscopy. Additionally, the nonlinear optical methods of two-photon excited fluorescence (TPEF) and coherent anti-Stokes Raman scattering (CARS) with infrared laser excitation were applied to study the localisation of SiNPs in cells. Advantages of the nonlinear methods, such as rapid imaging, which prevents cells from overheating and larger penetration depth compared to the single-photon excited HR-SIM, are discussed. The obtained results reveal new perspectives of the multimodal visualisation and precise detection of the uptake of biodegradable non-toxic SiNPs by cancer cells and they are discussed in view of future applications for the optical diagnostics of cancer tumours.

Topics: Humans; MCF-7 Cells; Microscopy; Multimodal Imaging; Nanowires; Neoplasms; Optical Imaging; Particle Size; Silicon; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis, Raman

Gold nanorods, DNA origami, and porous silicon nanoparticle-functionalized biocompatible double emulsion are developed for versatile molecular targeted therapeutics and antibody combination therapy. This advanced photothermal responsive all-in-one biocompatible platform can be easily formed with great therapeutics loading capacity for different cancer treatments with synergism and multidrug resistance inhibition, which has great potential in advancing biomedical applications.

Topics: Antibodies; DNA; Emulsions; Gold; Humans; Metal Nanoparticles; Nanomedicine; Nanotubes; Neoplasms; Silicon

Recent advances in the field of nanomedicine have demonstrated that biomimicry can further improve targeting properties of current nanotechnologies while simultaneously enable carriers with a biological identity to better interact with the biological environment. Immune cells for example employ membrane proteins to target inflamed vasculature, locally increase vascular permeability, and extravasate across inflamed endothelium. Inspired by the physiology of immune cells, we recently developed a procedure to transfer leukocyte membranes onto nanoporous silicon particles (NPS), yielding Leukolike Vectors (LLV). LLV are composed of a surface coating containing multiple receptors that are critical in the cross-talk with the endothelium, mediating cellular accumulation in the tumor microenvironment while decreasing vascular barrier function. We previously demonstrated that lymphocyte function-associated antigen (LFA-1) transferred onto LLV was able to trigger the clustering of intercellular adhesion molecule 1 (ICAM-1) on endothelial cells. Herein, we provide a more comprehensive analysis of the working mechanism of LLV in vitro in activating this pathway and in vivo in enhancing vascular permeability. Our results suggest the biological activity of the leukocyte membrane can be retained upon transplant onto NPS and is critical in providing the particles with complex biological functions towards tumor vasculature.

Topics: Animals; Biomimetic Materials; Cell Membrane; Drug Delivery Systems; Female; Human Umbilical Vein Endothelial Cells; Humans; Jurkat Cells; Leukocytes; Mice, Inbred BALB C; Nanopores; Neoplasms; Neovascularization, Pathologic; Silicon

The rearrangement of actin cytoskeleton is being increasingly considered a marker of cancer cell activity, but the fine structure and remodeling of microfilaments within tumor tissue still remains unclear.. We used the recently introduced silicon-rhodamine (SiR)-actin dye to visualize endogenous actin within tissues by confocal or total internal reflection fluorescence microscopy. We established imaging conditions for robust blinking of SiR-actin, which makes this dye applicable for super-resolution localization microscopy, as well as for an efficient background elimination.. We studied tumor tissue samples in two mouse models at high resolution and revealed a complex network of thick curved bundles of actin in cancer cells in tumors. This actin pattern differed strongly from that in cancer cells in vitro and in normal tissues.. Localization microscopy with SiR-actin provides an efficient way to visualize fine actin structure in tumor tissues. It is potentially applicable to a variety of biological and clinical samples.

Topics: Actins; Animals; Cell Line, Tumor; Colon; Coloring Agents; Female; Humans; Lung; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Microscopy, Fluorescence; Neoplasms; Rhodamines; Silicon; Staining and Labeling

We report on an ultrasensitive, molecularly modified silicon nanowire field effect transistor that brings together the lock-and-key and cross-reactive sensing worlds for the diagnosis of (gastric) cancer from exhaled volatolome. The sensor is able to selectively detect volatile organic compounds (VOCs) that are linked with gastric cancer conditions in exhaled breath and to discriminate them from environmental VOCs that exist in exhaled breath samples but do not relate to the gastric cancer per se. Using breath samples collected from actual patients with gastric cancer and from volunteers who do not have cancer, blind analysis validated the ability of the reported sensor to discriminate between gastric cancer and control conditions with >85% accuracy, irrespective of important confounding factors such as tobacco consumption and gender. The reported sensing approach paves the way to use the power of silicon nanowires for simple, inexpensive, portable, and noninvasive diagnosis of cancer and other disease conditions.

Topics: Breath Tests; Humans; Limit of Detection; Nanowires; Neoplasms; Silicon; Volatile Organic Compounds

Cancerous transformation may be dependent on correlation between electrical disruptions in the cell membrane and mechanical disruptions of cytoskeleton structures. Silicon nanotube (SiNT)-based electrical probes, as ultra-accurate signal recorders with subcellular resolution, may create many opportunities for fundamental biological research and biomedical applications. Here, we used this technology to electrically monitor cellular mechanosensing. The SiNT probe was combined with an electrically activated glass micropipette aspiration system to achieve a new cancer diagnostic technique that is based on real-time correlation between mechanical and electrical behaviour of single cells. Our studies demonstrated marked changes in the electrical response following increases in the mechanical aspiration force in healthy cells. In contrast, such responses were extremely weak for malignant cells. Confocal microscopy results showed the impact of actin microfilament remodelling on the reduction of the electrical response for aspirated cancer cells due to the significant role of actin in modulating the ion channel activity in the cell membrane.

Topics: Actin Cytoskeleton; Actins; Biosensing Techniques; Cell Line, Tumor; Cell Membrane; Cell Transformation, Neoplastic; Electricity; HT29 Cells; Humans; Ion Channels; Microscopy, Confocal; Nanotubes; Neoplasms; Silicon

An integrated translational biosensing technology based on arrays of silicon nanowire field-effect transistors (SiNW FETs) is described and has been preclinically validated for the ultrasensitive detection of the cancer biomarker ALCAM in serum. High-quality SiNW arrays have been rationally designed toward their implementation as molecular biosensors. The FET sensing platform has been fabricated using a complementary metal oxide semiconductor (CMOS)-compatible process. Reliable and reproducible electrical performance has been demonstrated via electrical characterization using a custom-designed portable readout device. Using this platform, the cancer prognostic marker ALCAM could be detected in serum with a detection limit of 15.5 pg/mL. Importantly, the detection could be completed in less than 30 min and span a wide dynamic detection range (∼10(5)). The SiNW-on-a-chip biosensing technology paves the way to the translational clinical application of FET in the detection of cancer protein markers.

Topics: Antigens, CD; Biomarkers, Tumor; Biosensing Techniques; Cell Adhesion Molecules, Neuronal; Fetal Proteins; Humans; Metals; Nanowires; Neoplasms; Oxides; Prognosis; Semiconductors; Silicon

Nanostructured porous silicon (PSi) is emerging as a promising platform for drug delivery owing to its biocompatibility, degradability and high surface area available for drug loading. The ability to control PSi structure, size and porosity enables programming its in vivo retention, providing tight control over embedded drug release kinetics. In this work, the relationship between the in vitro and in vivo degradation of PSi under (pre)clinically relevant conditions, using breast cancer mouse model, is defined. We show that PSi undergoes enhanced degradation in diseased environment compared with healthy state, owing to the upregulation of reactive oxygen species (ROS) in the tumour vicinity that oxidize the silicon scaffold and catalyse its degradation. We further show that PSi degradation in vitro and in vivo correlates in healthy and diseased states when ROS-free or ROS-containing media are used, respectively. Our work demonstrates that understanding the governing mechanisms associated with specific tissue microenvironment permits predictive material performance.

Topics: Animals; Cell Line, Tumor; Drug Carriers; Fluorescence; Humans; Mice; Nanostructures; Neoplasms; Porosity; Reactive Oxygen Species; Silicon; Tumor Microenvironment

Nanomaterials provide a unique platform for the development of theranostic systems that combine diagnostic imaging modalities with a therapeutic payload in a single probe. In this work, dual-labeled iRGD-modified multifunctional porous silicon nanoparticles (PSi NPs) were prepared from dibenzocyclooctyl (DBCO) modified PSi NPs by strain-promoted azide-alkyne cycloaddition (SPAAC) click chemistry. Hydrophobic antiangiogenic drug, sorafenib, was loaded into the modified PSi NPs to enhance the drug dissolution rate and improve cancer therapy. Radiolabeling of the developed system with (111)In enabled the monitoring of the in vivo biodistribution of the nanocarrier by single photon emission computed tomography (SPECT) in an ectopic PC3-MM2 mouse xenograft model. Fluorescent labeling with Alexa Fluor 488 was used to determine the long-term biodistribution of the nanocarrier by immunofluorescence at the tissue level ex vivo. Modification of the PSi NPs with an iRGD peptide enhanced the tumor uptake of the NPs when administered intravenously. After intratumoral delivery the NPs were retained in the tumor, resulting in efficient tumor growth suppression with particle-loaded sorafenib compared to the free drug. The presented multifunctional PSi NPs highlight the utility of constructing a theranostic nanosystems for simultaneous investigations of the in vivo behavior of the nanocarriers and their drug delivery efficiency, facilitating the selection of the most promising materials for further NP development.

Topics: Angiogenesis Inhibitors; Animals; Cell Line, Tumor; Humans; Male; Mice, Nude; Nanoparticles; Neoplasms; Niacinamide; Phenylurea Compounds; Silicon; Sorafenib; Theranostic Nanomedicine

Micro- and nanometer-size particles have become popular candidates for cancer vaccine adjuvants. However, the mechanism by which such particles enhance immune responses remains unclear. Here, we report a porous silicon microparticle (PSM)-based cancer vaccine that greatly enhances cross-presentation and activates type I interferon (IFN-I) response in dendritic cells (DCs). PSM-loaded antigen exhibited prolonged early endosome localization and enhanced cross-presentation through both proteasome- and lysosome-dependent pathways. Phagocytosis of PSM by DCs induced IFN-I responses through a TRIF- and MAVS-dependent pathway. DCs primed with PSM-loaded HER2 antigen produced robust CD8 T cell-dependent anti-tumor immunity in mice bearing HER2+ mammary gland tumors. Importantly, this vaccination activated the tumor immune microenvironment with elevated levels of intra-tumor IFN-I and MHCII expression, abundant CD11c+ DC infiltration, and tumor-specific cytotoxic T cell responses. These findings highlight the potential of PSM as an immune adjuvant to potentiate DC-based cancer immunotherapy.

Topics: Adaptor Proteins, Signal Transducing; Adaptor Proteins, Vesicular Transport; Animals; Antigens, Neoplasm; Cancer Vaccines; Cross-Priming; Dendritic Cells; Female; Immunity, Innate; Interferon Type I; Mammary Neoplasms, Animal; Mice, Inbred C57BL; Microspheres; Neoplasms; Ovalbumin; Phagocytosis; Porosity; Receptor, ErbB-2; Signal Transduction; Silicon; T-Lymphocytes, Cytotoxic; Tumor Microenvironment

We herein introduce a kind of fluorescent silicon nanoparticles (SiNPs) bioprobes, that is, peptides-conjugated SiNPs, which simultaneously feature small sizes (<10 nm), biological functionality, and stable and strong fluorescence (photoluminescent quantum yield (PLQY): ∼28%), as well as favorable biocompatibility. Taking advantage of these merits, we further demonstrate such resultant SiNPs bioprobes are superbly suitable for real-time immunofluorescence imaging of cancer cells. Meanwhile, malignant tumor cells could be specifically destroyed by the peptides-conjugated SiNPs, suggesting potential promise of simultaneous detection and treatment of cancer cells.

Topics: Humans; Nanoparticles; Neoplasms; Peptides; Silicon; Spectrophotometry, Ultraviolet

Applications of biomaterials in cancer therapy has been limited to drug delivery systems and markers in radiation therapy. In this article, we introduce the concept of phase-functionalization of silicon to preferentially select cancer cell populations for survival in a catalyst and additive free approach. Silicon is phase-functionalized by the interaction of ultrafast laser pulses, resulting in the formation of rare phases of SiO2 in conjunction with differing silicon crystal lattices. The degree of phase-functionalization is programmed to dictate the degree of repulsion of cancer cells. Unstable phases of silicon oxides are synthesized during phase-functionalization and remain stable at ambient conditions. This change in phase of silicon as well as formation of oxides contributes to changes in surface chemistry as well as surface energy. These material properties elicit in precise control of migration, cytoskeleton shape, direction and population. To the best of our knowledge, phase-functionalized silicon without any changes in topology or additive layers and its applications in cancer therapy has not been reported before. This unique programmable phase-functionalized silicon has the potential to change current trends in cancer research and generate focus on biomaterials as cancer repelling or potentially cancer killing surfaces.

Topics: Actin Cytoskeleton; Biocompatible Materials; Cell Line, Tumor; Cell Nucleus; Drug Delivery Systems; Humans; Models, Theoretical; Nanotechnology; Neoplasms; Pseudopodia; Silicon

We generated low-flux X-ray micro-planar beams (MPBs) using a laboratory-scale industrial X-ray generator (60 kV/20 mA) with custom-made collimators with three different peak/pitch widths (50/200 μm, 100/400 μm, 50/400 μm). To evaluate normal skin reactions, the thighs of C3H/HeN mice were exposed to 100 and 200 Gy MPBs in comparison with broad beams (20, 30, 40, 50, 60 Gy). Antitumor effects of MPBs were evaluated in C3H/HeN mice with subcutaneous tumors (SCCVII). After the tumors were irradiated with 100 and 200 Gy MPBs and 20 and 30 Gy broad beams, the tumor sizes were measured and survival analyses were performed. In addition, the tumors were excised and immunohistochemically examined to detect γ-H2AX, ki67 and CD34. It was shown that antitumor effects of 200 Gy MPBs at 50/200 μm and 100/400 μm were significantly greater than those of 20 Gy broad beams, and were comparable with 30 Gy broad beams. γ-H2AX-positive cells demonstrated clear stripe-patterns after MPB irradiation; the pattern gradually faded and intermixed over 24 h. The chronological changes in ki67 positivity did not differ between MPBs and broad beams, whereas the CD34-positive area decreased significantly more in MPBs than in broad beams. In addition, it was shown that skin injury after MPB irradiation was significantly milder when compared with broad-beam irradiation at equivalent doses for achieving the same tumor control effect. Bystander effect and tumor vessel injury may be the mechanism contributing to the efficacy of MPBs.

Topics: Animals; Antigens, CD34; Bystander Effect; Carcinoma, Squamous Cell; Dermatitis; Dose-Response Relationship, Radiation; Equipment Design; Immunohistochemistry; Ki-67 Antigen; Mice; Mice, Inbred C3H; Neoplasm Transplantation; Neoplasms; Radiation Injuries; Radiometry; Silicon; Skin; Time Factors; X-Rays

Currently, the use of nano silicon in cancer therapy is limited as drug delivery vehicles and markers in imaging, not as manipulative/controlling agents. This is due to limited properties that native states of nano silicon and silicon oxides offers. We introduce nano-functionalized multi-phased silicon/silicon oxide biomaterials synthesized via ultrashort pulsed laser synthesis, with tunable properties that possess inherent cancer controlling properties that can passivate the progression of cancer. This nanostructured biomaterial is composed of individual functionalized nanoparticles made of a homogenous hybrid of multiple phases of silicon and silicon oxide in increasing concentration outwards from the core. The chemical properties of the proposed nanostructure such as number of phases, composition of phases and crystal orientation of each functionalized nanoparticle in the three dimensional nanostructure is defined based on precisely tuned ultrashort pulsed laser-material interaction mechanisms. The amorphous rich phased biomaterial shows a 30 fold (95%) reduction in number of cancer cells compared to bulk silicon in 48 hours. Further, the size of the cancer cells reduces by 76% from 24 to 48 hours. This method exposes untapped properties of combination of multiple phases of silicon oxides and its applications in cancer therapy.

Topics: Biocompatible Materials; Cell Adhesion; Cell Death; Cell Proliferation; Humans; Nanostructures; Neoplasms; Silicon; Silicon Dioxide

The Silicon-Fluoride-Acceptor (SiFA)-(18)F-labeling strategy has been shown before to enable the straightforward and efficient (18)F-labeling of complex biologically active substances such as proteins and peptides. Especially in the case of peptides, the radiolabeling proceeds kit-like in short reaction times and without the need of complex product workup. SiFA-derivatized, (18)F-labeled Tyr(3)-octreotate (TATE) derivatives demonstrated, besides strong somatostatin receptor (SSTR) binding, favorable in vivo pharmacokinetics as well as excellent tumor visualization by PET imaging. In this study, we intended to determine the influence of the underlying molecular design and used molecular scaffolds of SiFAlin-TATE derivatives on SSTR binding as well as on the in vivo pharmacokinetics of the resulting (18)F-labeled peptides. For this purpose, new SiFAlin-(Asp)n-PEG1-TATE analogs (where n = 1-4) were synthesized, efficiently radiolabeled with (18)F in a kit-like manner and obtained in radiochemical yields of 70-80%, radiochemical purities of ≥97%, and nonoptimized specific activities of 20.1-45.2 GBq/μmol within 20-25 min starting from 0.7-1.5 GBq of (18)F. In the following, the radiotracer's lipophilicities and stabilities in human serum were determined. Furthermore, the SSTR-specific binding affinities were evaluated by a competitive displacement assay on SSTR-positive AR42J cells. The obtained in vitro results support the assumption that aspartic acids are able to considerably increase the radiotracer's hydrophilicity and that their number does not affect the SSTR binding potential of the TATE derivatives. The most promising tracer (18)F-SiFAlin-Asp3-PEG1-TATE [(18)F]6 (LogD = -1.23 ± 0.03, IC50 = 20.7 ± 2.5 nM) was further evaluated in vivo in AR42J tumor-bearing nude mice via PET/CT imaging against the clinical gold standard (68)Ga-DOTATATE as well as the previously developed SiFAlin-TATE derivative [(18)F]3. The results of these evaluations showed that [(18)F]6-although showing very similar chemical and in vitro properties to [(18)F]3-exhibits not only a slowed renal clearance compared to [(18)F]3, but also a higher absolute tumor uptake compared to (68)Ga-DOTATATE, and furthermore enables excellent tumor visualization with high image resolution. These results emphasize the importance of systematic study of the influence of molecular design and applied structure elements of peptidic radiotracers, as these may considerably influence in vivo pharmacokineti

Topics: Animals; Cell Line; Cell Line, Tumor; Fluorides; Fluorine Radioisotopes; Humans; Mice, Nude; Models, Molecular; Neoplasms; Peptides, Cyclic; Positron-Emission Tomography; Receptors, Somatostatin; Silicon

A direct, rapid, highly sensitive and specific biosensor for detection of cancer biomarkers is desirable in early diagnosis and prognosis of cancer. However, the existing methods of detecting cancer biomarkers suffer from poor sensitivity as well as the requirement of enzymatic labeling or nanoparticle conjugations. Here, we proposed a two-channel PDMS microfluidic integrated CMOS-compatible silicon nanowire (SiNW) field-effect transistor arrays with potentially single use for label-free and ultrasensitive electrical detection of cancer biomarkers. The integrated nanowire arrays showed not only ultrahigh sensitivity of cytokeratin 19 fragment (CYFRA21-1) and prostate specific antigen (PSA) with detection to at least 1 fg/mL in buffer solution but also highly selectivity of discrimination from other similar cancer biomarkers. In addition, this method was used to detect both CYFRA21-1 and PSA real samples as low as 10 fg/mL in undiluted human serums. With its excellent properties and miniaturization, the integrated SiNW-FET device opens up great opportunities for a point-of-care test (POCT) for quick screening and early diagnosis of cancer and other complex diseases.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Humans; Kallikreins; Keratin-19; Microfluidic Analytical Techniques; Nanowires; Neoplasms; Prostate-Specific Antigen; Silicon

Porous silicon (PSi) has been demonstrated as a promising drug delivery vector for poorly water-soluble drugs. Here, a simple and efficient method based on copper-free click chemistry was used to introduce targeting moieties to PSi nanoparticles in order to enhance the intracellular uptake and tumor specific targeting hydrophobic drug delivery. Two RGD derivatives (RGDS and iRGD) with azide-terminated groups were conjugated to bicyclononyne-functionalized PSi nanoparticles via copper-free azide-alkyne cycloaddition. The surface functionalization was performed in aqueous solution at 37 °C for 30 min resulting in conjugation efficiencies of 15.2 and 3.4% (molar ratios) and the nanoparticle size increased from 165.6 nm to 179.6 and 188.8 nm for RGDS and iRGD, respectively. The peptides modification enhanced the cell uptake efficiency of PSi nanoparticles in EA.hy926 cells. PSi-RGDS and PSi-iRGD nanoparticles loaded with sorafenib showed a similar trend for the in vitro antiproliferation activity compared to sorafenib dissolved in dimethyl sulfoxide. Furthermore, sorafenib-loaded PSi-RGDS deliver the drug intracellulary efficiently due to the higher surface conjugation ratio, resulting in enhanced in vitro antiproliferation effect. Our results highlight the surface functionalization methodology for PSi nanoparticles applied here as a universal method to introduce functional moieties onto the surface of PSi nanoparticles and demonstrate their potential active targeting properties for anticancer drug delivery.

Topics: Alkynes; Antineoplastic Agents; Azides; Cell Line, Tumor; Cell Proliferation; Click Chemistry; Cycloaddition Reaction; Drug Carriers; Humans; Nanoparticles; Neoplasms; Niacinamide; Phenylurea Compounds; Porosity; Silicon; Sorafenib

We report on the rapid and direct quantification of specific cell captures using a micro-patterned streptavidin (STR)-functionalized silicon nanowire (SiNW) platform, which was prepared by Ag-assisted wet chemical etching and a photo-lithography process. This platform operates by high-affinity cell capture rendered by the combination of antibody-epithelial cell surface-binding, biotin-streptavidin binding, and the topologically enhanced cell-substrate interaction on a 3-dimensional SiNWs array. In this work, we developed a micro-patterned nanowire platform, with which we were able to directly evaluate the performance enhancement due to nanotopography. An excellent capture efficiency of ~96.6±6.7%, which is the highest value achieved thus far for the targeting specific A549 cells on a selective area of patterned SiNWs, is demonstrated. Direct comparison between the nanowire region and the planar region on the same substrate indicates dramatically elevated cell-capture efficiency on nanotopological surface identical surface chemistry (<2% cell-capture efficiency). An excellent linear response was seen for quantifying captured A549 cells with respect to loaded cells. This study suggests that the micro-patterned STR-functionalized SiNWs platform provides additional advantage for detecting rare cells populations in a more quantitative and specific manner.

Topics: Biosensing Techniques; Biotin; Cell Line, Tumor; Cell Separation; Humans; Nanowires; Neoplasms; Protein Binding; Silicon; Streptavidin; Surface Properties; Tissue Array Analysis

Porous silicon has been used for the delivery of therapeutic and imaging agents in several biomedical applications. Here, mesoporous silicon nanoconstructs (SiMPs) with a discoidal shape and a sub-micrometer size (1000×400nm) have been conjugated with gadolinium-tetraazacyclododecane tetraacetic acid Gd(DOTA) molecules and proposed as contrast agents for Magnetic Resonance Imaging. The surface of the SiMPs with different porosities - small pore (SP: ∼5nm) and huge pore (HP: ∼40nm) - and of bulk, non-porous silica beads (1000nm in diameter) have been modified with covalently attached (3-aminopropyl)triethoxysilane (APTES) groups, conjugated with DOTA molecules, and reacted with an aqueous solution of GdCl3. The resulting Gd(DOTA) molecules confined within the small pores of the Gd-SiMPs achieve longitudinal relaxivities r1 of ∼17 (mMs)(-)(1), which is 4 times greater than for free Gd(DOTA). This enhancement is ascribed to the confinement and stable chelation of Gd(DOTA) molecules within the SiMP mesoporous matrix. The resulting nanoconstructs possess no cytotoxicity and accumulate in ovarian tumors up to 2% of the injected dose per gram tissue, upon tail vein injection. All together this data suggests that Gd-SiMPs could be efficiently used for MR vascular imaging in cancer and other diseases.

Topics: Contrast Media; Heterocyclic Compounds; Humans; Magnetic Resonance Imaging; Molecular Structure; Nanoparticles; Neoplasms; Organometallic Compounds; Porosity; Silicon

The use of nanoparticle carriers for the sustained release of cytotoxic drugs in cancer therapy can result in fewer adverse effects and can thus be of great benefit for the patient. Recently, a novel nanocomposite, prepared by the encapsulation of THCPSi nanoparticles within solid lipids (SLN), was developed and characterized as a promising drug delivery carrier in vitro. The present study describes the in vivo evaluation of unmodified THCPSi nanoparticles and THCPSi-solid lipid nanocomposites (THCPSi-SLNCs) as potential drug delivery carriers for cancer therapy by using (18)F radiolabeling for the detection of the particle biodistribution in mice. Passive tumor targeting of (18)F-THCPSis and (18)F-THCPSi-SLNCs by the enhanced permeation and retention effect was investigated in a murine breast cancer model. Encapsulation of THCPSi nanoparticles with solid lipids improved their accumulation in tumors at a 7 week time point (tumor-to-liver ratio 0.10 ± 0.08 and 0.24 ± 0.09% for (18)F-THCPSis and (18)F-THCPSi-SLNCs, respectively).

Topics: Animals; Autoradiography; Cell Line, Tumor; Disease Models, Animal; Drug Carriers; Female; Humans; Infusions, Intravenous; Lipids; Liver; Mammary Neoplasms, Experimental; Mice; Microscopy, Electron, Transmission; Nanocomposites; Nanoparticles; Nanotechnology; Neoplasms; Porosity; Serum Albumin, Bovine; Silicon; Time Factors; Tissue Distribution

A class of stem-loop DNA-assisted silicon nanowires (SiNWs)-based fluorescent biosensor is presented in this report. Significantly, the sensor enables rapid and sensitive detection of DNA targets with a concentration as low as 1 pM. Moreover, the large planar surface of SiNWs facilitates simultaneous assembly with different DNA strands, which is favorable for multiplexed DNA detection. On the other hand, the SiNWs-based sensor is highly efficacious for detecting heavy metal ions. Mercury ions (Hg(2+)) of low concentrations (e.g., 5 pM) are readily identified from its mixture with over 10 kinds of interfering metal ions, even in real water samples. Given that SiNWs can be fabricated in a facile, reproducible and low-cost manner, this kind of SiNWs-based high-performance sensor is expected to be a practical analytical tool for a variety of biological and environment-protection applications.

Topics: Calibration; Coloring Agents; DNA; Genes, Tumor Suppressor; Humans; Ions; Kinetics; Mercury; Metal Nanoparticles; Metals; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Nanotechnology; Nanowires; Neoplasms; Organic Chemicals; Silicon; Spectrometry, Fluorescence; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared

While substrates with nanopillars (NPs) have emerged as promising platforms for isolation of circulating tumor cells (CTCs), the influence of diameter and spacing of NPs on CTC capture is still unclear. In this paper, CTC-capture yield and cell behaviors have been investigated by using antibody functionalized NPs of various diameters (120-1100 nm) and spacings (35-800 nm). The results show a linear relationship between the cell capture yield and effective contact area of NP substrates where a NP array of small diameter and reasonable spacing is preferred; however, spacing that is too small or too large adversely impairs the capture efficiency and specificity, respectively. In addition, the formation of pseudopodia between captured cells and the substrate is found to be dependent not only on cell adhesion status but also on elution strength and shear direction. These findings provide essential guidance in designing NP substrates for more efficient capture of CTCs and manipulation of cytomorphology in future.

Topics: Antigens, Neoplasm; Cell Adhesion; Cell Adhesion Molecules; Cell Line, Tumor; Epithelial Cell Adhesion Molecule; Humans; Linear Models; Microscopy, Electron, Scanning; Nanoparticles; Nanotechnology; Neoplasms; Neoplastic Cells, Circulating; Pseudopodia; Shear Strength; Silicon; Stress, Mechanical; Surface Properties; Wettability

There is an increasing awareness that health care must move from post-symptomatic treatment to presymptomatic intervention. An ideal system would allow regular inexpensive monitoring of health status using circulating antibodies to report on health fluctuations. Recently, we demonstrated that peptide microarrays can do this through antibody signatures (immunosignatures). Unfortunately, printed microarrays are not scalable. Here we demonstrate a platform based on fabricating microarrays (~10 M peptides per slide, 330,000 peptides per assay) on silicon wafers using equipment common to semiconductor manufacturing. The potential of these microarrays for comprehensive health monitoring is verified through the simultaneous detection and classification of six different infectious diseases and six different cancers. Besides diagnostics, these high-density peptide chips have numerous other applications both in health care and elsewhere.

Topics: Amino Acid Sequence; Antibodies, Monoclonal; Antibody Specificity; Communicable Diseases; Health Status; Humans; Lab-On-A-Chip Devices; Microtechnology; Molecular Sequence Data; Monitoring, Physiologic; Neoplasms; Peptides; Protein Array Analysis; Quality Control; Silicon

Response of pMOS dosemeters during two successive irradiations with gamma-ray irradiation to a dose of 35 Gy and annealing at room and elevated temperature has been studied. The response was followed on the basis of threshold voltage shift, determined from transfer characteristics, as a function of absorbed dose or annealing time. It was shown that the threshold voltage shifts during first and second irradiation for the gate bias during irradiation of 5 and 2.5 V insignificantly differ although complete fading was not achieved after the first cycle of annealing. In order to analyse the defects formed in oxide and at the interface during irradiation and annealing, which are responsible for threshold voltage shift, midgap and charge-pumping techniques were used. It was shown that during first irradiation and annealing a dominant influence to threshold voltage shift is made by fixed oxide traps, while at the beginning of the second annealing cycle, threshold voltage shift is a consequence of both fixed oxide traps and slow switching traps.

Topics: Equipment Design; Gamma Rays; Humans; Neoplasms; Radiation Dosage; Radiometry; Radiotherapy; Silicon; Silicon Dioxide; Temperature

The applicability of ultrasmall uncapped and aminosilanized oxidized silicon nanoparticles (SiNPs and NH2-SiNPs) as radiosensitizer was studied by internalizing these nanoparticles into human breast cancer (MCF-7) and mouse fibroblast cells (3T3) that were exposed to X-rays at a single dose of 3 Gy. While SiNPs did not increase the production of reactive oxygen species (ROS) in X-ray treated cells, the NH2-SiNPs significantly enhanced the ROS formation. This is due to the amino functionality as providing positive surface charges in aqueous environment. The NH2-SiNPs were observed to penetrate into the mitochondrial membrane, wherein these nanoparticles provoked oxidative stress. The NH2-SiNPs induced mitochondrial ROS production was confirmed by the determination of an increased malondialdehyde level as representing a gauge for the extent of membrane lipid peroxidation. X-ray exposure of NH2-SiNPs incubated MCF-7 and 3T3 cells increased the ROS concentration for 180%, and 120%, respectively. Complementary cytotoxicity studies demonstrate that these silicon nanoparticles are more cytotoxic for MCF-7 than for 3T3 cells.

Topics: 3T3 Cells; Animals; Antineoplastic Agents; Cell Survival; Cytosol; Drug Screening Assays, Antitumor; Humans; MCF-7 Cells; Mice; Microscopy, Electron, Transmission; Mitochondria; Mitochondrial Membranes; Nanoparticles; Nanotechnology; Neoplasms; Oxidation-Reduction; Oxidative Stress; Particle Size; Radiation-Sensitizing Agents; Reactive Oxygen Species; Silicon; X-Rays

Here, we first present an isothermal solid-phase amplification/detection (ISAD) technique for the detection of single-point mutations that can be performed without labelling in real-time by utilizing both silicon microring-based solid-phase amplification and isothermal recombinase polymerase amplification (RPA). The ISAD technique was performed on a silicon microring device with a plastic chamber containing 10 μL of the reaction mixture, and characterized with an assay for the detection of the HRAS (Harvey RAS) gene single-point mutation. For the solid-phase amplification, the primer of the gene was directly attached to the surface of the device via an amine modification reaction. The amplified DNA was detected, without a label, by measuring the optical wavelength shift of the silicon microring resonator during the reaction. We demonstrated that the sensitivity of the ISAD technique was 100-times higher than that of RPA and conventional PCR methods. Moreover, this technique can be used to distinguish a single-point mutation of the HRAS gene via target amplification. This novel DNA amplification/detection technique will be useful for the detection of sequence alterations such as mutations and single-nucleotide polymorphisms as DNA biomarkers in human diseases.

Topics: DNA, Neoplasm; Humans; Neoplasms; Nucleic Acid Amplification Techniques; Point Mutation; Polymerase Chain Reaction; Proto-Oncogene Proteins p21(ras); Recombinases; Silicon; Temperature; Time Factors

A series of novel silicon(IV) phthalocyanines conjugated axially with different nucleoside moieties (uridine, 5-methyluridine, cytidine, and 5-N-cytidine derivatives) have been synthesized and evaluated for their photodynamic activities. The uridine-containing compound 1 exhibits the highest photocytotoxicity against HepG2 human hepatocarcinoma cells with an IC50 value as low as 6 nM, which can be attributed to its high cellular uptake and non-aggregated nature in the biological media. This compound shows high affinity toward the mitochondria of HepG2 cells and causes cell death mainly through apoptosis upon illumination. The result indicates that 1 is a highly promising photosensitizer for photodynamic therapy.

Topics: Apoptosis; Coordination Complexes; Hep G2 Cells; Humans; Indoles; Isoindoles; Microscopy, Confocal; Neoplasms; Nucleosides; Photochemotherapy; Photosensitizing Agents; Silicon

It is now well established that tumor cell invasion through tissue is strongly regulated by the microstructural and mechanical properties of the extracellular matrix (ECM). However, it remains unclear how these physical microenvironmental inputs are jointly processed with oncogenic lesions to drive invasion. In this study, we address this open question by combining a microfabricated polyacrylamide channel (μPAC) platform that enables independent control of ECM stiffness and confinement with an isogenically-matched breast tumor progression series in which the oncogenes ErbB2 and 14-3-3ζ are overexpressed independently or in tandem. We find that increasing channel confinement and overexpressing ErbB2 both promote cell migration to a similar degree when other parameters are kept constant. In contrast, 14-3-3ζ overexpression slows migration speed, and does so in a fashion that dwarfs effects of ECM confinement and stiffness. We also find that ECM stiffness dramatically enhances cell motility when combined with ErbB2 overexpression, demonstrating that biophysical cues and cell-intrinsic parameters promote cell invasion in an integrative manner. Morphometric analysis of cells inside the μPAC platform reveals that the rapid cell migration induced by narrow channels and ErbB2 overexpression are both accompanied by increased cell polarization. Disruption of this polarization occurs by pharmacological inhibition of Rac GTPase phenocopies 14-3-3ζ overexpression by reducing cell polarization and slowing migration. By systematically measuring migration speed as a function of matrix stiffness and confinement, we also quantify for the first time the sensitivity of migration speed to microchannel properties and transforming potential. These results demonstrate that oncogenic lesions and ECM biophysical properties can synergistically interact to drive invasive migration, and that both inputs may act through common molecular mechanisms to enhance migration speed.

Topics: 14-3-3 Proteins; Acrylic Resins; Cell Culture Techniques; Cell Line, Tumor; Cell Movement; Cell Transformation, Neoplastic; Extracellular Matrix; Humans; Hydrogel, Polyethylene Glycol Dimethacrylate; Microscopy, Confocal; Microscopy, Phase-Contrast; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; rac GTP-Binding Proteins; Receptor, ErbB-2; Silicon

Tumour targeting nanoparticles (NPs) have demonstrated great potential for enhancing anticancer drug delivery to tumour sites and for reducing the side effects of chemotherapy. However, many nanoparticulate delivery systems still lack efficient tumour accumulation. In this work, we present a porous silicon (PSi) nanovector functionalized with a tumour-homing peptide, which targets the mammary-derived growth inhibitor (MDGI) expressing cancer cells both in vitro and in vivo, thereby enhancing the accumulation of the NPs in the tumours. We demonstrated that the tumour homing peptide (herein designated as CooP) functionalized thermally hydrocarbonized PSi (THCPSi) NPs homed specifically to the subcutaneous MDGI-expressing xenograft tumours. The THCPSi-CooP NPs were stable in human plasma and their uptake by MDGI-expressing cancer cells measured by confocal microscopy and flow cytometry was significantly increased compared to the non-functionalized THCPSi NPs. After intravenous injections into nude mice bearing MDGI-expressing tumours, effective targeting was detected and THCPSi-CooP NPs showed ~9-fold higher accumulation in the tumour site compared to the control THCPSi NPs. Accumulation of both NPs in the vital organs was negligible.

Topics: Adsorption; Animals; Blood Proteins; Cell Line, Tumor; Cell Survival; Drug Delivery Systems; Fatty Acid-Binding Proteins; Female; Flow Cytometry; Humans; Mice; Mice, Inbred BALB C; Nanoparticles; Neoplasms; Peptides; Porosity; Silicon; Spectroscopy, Fourier Transform Infrared; Tissue Distribution

Topics: Animals; Antibiotics, Antineoplastic; Cell Line, Tumor; Cell Survival; Doxorubicin; Drug Carriers; HeLa Cells; Humans; Hydrogen-Ion Concentration; Mice; Mice, Nude; Nanowires; Neoplasms; Silicon; Transplantation, Heterologous

Near-infrared (NIR) hyperthermia agents are of current interest because they hold great promise as highly efficacious tools for cancer photothermal therapy. Although various agents have been reported, a practical NIR hyperthermia agent is yet unavailable. Here, we present the first demonstration that silicon nanomaterials-based NIR hyperthermia agent, that is, gold nanoparticles-decorated silicon nanowires (AuNPs@SiNWs), is capable of high-efficiency destruction of cancer cells. AuNPs@SiNWs are found to possess strong optical absorbance in the NIR spectral window, producing sufficient heat under NIR irradiation. AuNPs@SiNWs are explored as novel NIR hyperthermia agents for photothermal ablation of tumor cells. In particular, three different cancer cells treated with AuNPs@SiNWs were completely destructed within 3 min of NIR irradiation, demonstrating the exciting potential of AuNPs@SiNWs for NIR hyperthermia agents.

Topics: Antineoplastic Agents; Cell Survival; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Gold; HeLa Cells; Humans; KB Cells; Lasers; Metal Nanoparticles; Nanowires; Neoplasms; Particle Size; Photochemotherapy; Photosensitizing Agents; Silicon; Spectroscopy, Near-Infrared; Structure-Activity Relationship; Surface Properties; Time Factors; Tumor Cells, Cultured

Silicon nanoparticles (SiNPs) obtained by mechanical grinding of porous silicon have been used for visualization of living cells in vitro. It was found that SiNPs could penetrate into the cells without any cytotoxic effect up to the concentration of 100 μg/ml. The cell cytoplasm was observed to be filled by SiNPs, which exhibited bright photoluminescence at 1.6 eV. SiNPs could also act as photosensitizers of the singlet oxygen generation, which could be used in the photodynamic therapy of cancer. These properties of SiNPs are discussed in view of possible applications in theranostics (both in therapy and in diagnostics).

Topics: Animals; Biocompatible Materials; Cell Survival; Dogs; Hep G2 Cells; Humans; Luminescent Agents; Luminescent Measurements; Mechanical Phenomena; Metal Nanoparticles; Mice; Molecular Imaging; Nanotechnology; Neoplasms; NIH 3T3 Cells; Photosensitizing Agents; Silicon; Singlet Oxygen; Water

Quantum dots (QDs) have size-dependent optical properties that make them uniquely advantageous for in vivo targeted fluorescence imaging, traceable delivery, and therapy. The use of group II-VI (e.g., CdSe) QDs for these applications is advancing rapidly. However, group II-VI QDs contain toxic heavy metals that limit their in vivo applications. Thus, replacing these with QDs of a biocompatible semiconductor, such as silicon (Si), is desirable. Here, we demonstrate that properly encapsulated biocompatible Si QDs can be used in multiple cancer-related in vivo applications, including tumor vasculature targeting, sentinel lymph node mapping, and multicolor NIR imaging in live mice. This work overcomes dispersibility and functionalization challenges to in vivo imaging with Si QDs through a unique nanoparticle synthesis, surface functionalization, PEGylated micelle encapsulation, and bioconjugation process that produces bright, targeted nanospheres with stable luminescence and long (>40 h) tumor accumulation time in vivo. Upon the basis of this demonstration, we anticipate that Si QDs can play an important role in more sophisticated in vivo models, by alleviating QD toxicity concerns while maintaining the key advantages of QD-based imaging methods.

Topics: Animals; Cell Line, Tumor; Color; Female; Humans; Lymph Nodes; Materials Testing; Metal Nanoparticles; Mice; Micelles; Molecular Imaging; Neoplasms; Particle Size; Silicon; Surface Properties

We report the real-time, label-free and electrical detection of vascular endotherial growth factor (VEGF) for cancer diagnosis using anti-VEGF aptamer-modified Si nanowire field-effect transistors (SiNW-FETs). Specifically, the high quality single-crystalline SiNWs of both n-type and p-type characters were surface modified with the covalent immobilization of anti-VEGF aptamers, and they were turned into SiNW-FET biosensors for the VEGF detection. We show that the VEGF molecules consistently act on the gate dielectrics of both n-type and p-type SiNW-FETs as electrically positive point-charges; their recognition to anti-VEGF aptamers depletes (accumulates) the charge carriers in the p-type (n-type) SiNW-FETs and thus decreases (increases) the detection currents. The detection limit for VEGFs in this study was determined as 1.04nM and 104pM for the cases of n-type and p-type SiNW-FETs, respectively.

Topics: Aptamers, Peptide; Biomarkers, Tumor; Biosensing Techniques; Electrochemistry; Equipment Design; Equipment Failure Analysis; Immunoassay; Nanotechnology; Nanotubes; Neoplasm Proteins; Neoplasms; Reproducibility of Results; Sensitivity and Specificity; Silicon; Transistors, Electronic; Vascular Endothelial Growth Factor A

Parameter studies, design calculations and initial neutronic performance measurements have been completed for a new thermal neutron beamline to be used for neutron capture therapy cell and small-animal radiobiology studies at the University of Missouri Research Reactor. The beamline features the use of single-crystal silicon and bismuth sections for neutron filtering and for reduction of incident gamma radiation. The calculated and measured thermal neutron fluxes produced at the irradiation location are 9.6 x 10(8) and 8.8 x 10(8)neutrons/cm(2)s, respectively. Calculated and measured cadmium ratios (Au foils) are 217 and 132. These results indicate a well-thermalized neutron spectrum with sufficient thermal neutron flux for a variety of small animal BNCT studies.

Topics: Animals; Bismuth; Boron Neutron Capture Therapy; Crystallization; Equipment Design; Fast Neutrons; Humans; Missouri; Neoplasms; Nuclear Reactors; Silicon

The physical behaviors of stationary cells, such as the morphology, motility, adhesion, anchorage, invasion and metastasis, are likely to be important for governing their biological characteristics. A change in the physical properties of mammalian cells could be an indication of disease. In this paper, we present a silicon-nanowire-array based technique for quantifying the mechanical behavior of single cells representing three distinct groups: normal mammalian cells, benign cells (L929), and malignant cells (HeLa). By culturing the cells on top of NW arrays, the maximum traction forces of two different tumor cells (HeLa, L929) have been measured by quantitatively analyzing the bending of the nanowires. The cancer cell exhibits a larger traction force than the normal cell by approximately 20% for a HeLa cell and approximately 50% for a L929 cell. The traction forces have been measured for the L929 cells and mechanocytes as a function of culture time. The relationship between cells extending area and their traction force has been investigated. Our study is likely important for studying the mechanical properties of single cells and their migration characteristics, possibly providing a new cellular level diagnostic technique.

Topics: Animals; Biophysical Phenomena; Cell Adhesion; Cell Line; Cell Line, Tumor; Cells, Cultured; HeLa Cells; Humans; Microscopy, Electron, Scanning; Models, Biological; Nanowires; Neoplasms; Silicon

Recent advances in label-free biosensing techniques have shown the potential to simplify clinical analyses. With this motivation in mind, this paper demonstrates for the first time the use of silicon-on-insulator microring optical resonator arrays for the robust and label-free detection of a clinically important protein biomarker in undiluted serum, using carcinoembryonic antigen (CEA) as the test case. We utilize an initial-slope-based quantitation method to sensitively detect CEA at clinically relevant levels and to determine the CEA concentrations of unknown samples in both buffer and undiluted fetal bovine serum. Comparison with a commercial enzyme-linked immunosorbent assay (ELISA) kit reveals that the label-free microring sensor platform has a comparable limit of detection (2 ng/mL) and superior accuracy in the measurement of CEA concentration across a 3 order of magnitude dynamic range. Notably, we report the lowest limit of detection to date for a microring resonator sensor applied to a clinically relevant cancer biomarker. Although this report describes the robust biosensing capabilities of silicon photonic microring resonator arrays for a single parameter assay, future work will focus on utilizing the platform for highly multiplexed, label-free bioanalysis.

Topics: Antibodies; Biosensing Techniques; Carcinoembryonic Antigen; Chemistry Techniques, Analytical; Humans; Micro-Electrical-Mechanical Systems; Neoplasms; Optics and Photonics; Silicon

Silicon sensor technologies, developed during the 1990s, allow measurement of extracellular chemical changes related to cell metabolism. Exposition of tumor cells in vitro to anticancer drugs modifies cell metabolism, making it possible to detect on-line with sensor chips patterns of metabolic activity, which depend on drug sensitivity, or drug resistance of the cells. Sensor devices are composed of an incubation chamber with a sensor chip and a fluidic system for medium supply. Basically, two sensor types are available: (1) monosensor systems to detect extracellular acidification; and (2) multisensor arrays for many parameters such as pH, oxygen consumption, and impedance. Two companies have developed such systems: Molecular Devices (USA) and Bionas (Germany). In this chapter, in addition to operation of the sensor devices, we describe techniques for tissue (tumor and non-tumor) preparation. Basically, three procedures are described: (1) tissue dissociation and further cultivation on the sensor chip or on Transwell inserts; (2) preparation of tissue slices (300 microm thick) and attachment to the sensor chip or to inserts, and (3) cultivation of cells in dialysis tubes, a procedure necessary for nonadherent cells and cell suspensions to avoid their washing away. Evaluation of results and selection of controls are also discussed.

Topics: Antineoplastic Agents; Biosensing Techniques; Cell Adhesion; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Electric Impedance; Electrodes; Humans; Hydrogen-Ion Concentration; Neoplasms; Oxygen; Oxygen Consumption; Silicon; Software; Time Factors; Transducers

Metal nanoshells are a class of nanoparticles with tunable optical resonances. In this article, an application of this technology to thermal ablative therapy for cancer is described. By tuning the nanoshells to strongly absorb light in the near infrared, where optical transmission through tissue is optimal, a distribution of nanoshells at depth in tissue can be used to deliver a therapeutic dose of heat by using moderately low exposures of extracorporeally applied near-infrared (NIR) light. Human breast carcinoma cells incubated with nanoshells in vitro were found to have undergone photothermally induced morbidity on exposure to NIR light (820 nm, 35 W/cm2), as determined by using a fluorescent viability stain. Cells without nanoshells displayed no loss in viability after the same periods and conditions of NIR illumination. Likewise, in vivo studies under magnetic resonance guidance revealed that exposure to low doses of NIR light (820 nm, 4 W/cm2) in solid tumors treated with metal nanoshells reached average maximum temperatures capable of inducing irreversible tissue damage (DeltaT = 37.4 +/- 6.6 degrees C) within 4-6 min. Controls treated without nanoshells demonstrated significantly lower average temperatures on exposure to NIR light (DeltaT < 10 degrees C). These findings demonstrated good correlation with histological findings. Tissues heated above the thermal damage threshold displayed coagulation, cell shrinkage, and loss of nuclear staining, which are indicators of irreversible thermal damage. Control tissues appeared undamaged.

Topics: Animals; Cell Line, Tumor; Female; Gold; Humans; Hyperthermia, Induced; Infrared Rays; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Mice; Mice, SCID; Models, Statistical; Nanotechnology; Neoplasms; Silicon; Temperature

The stability in a biological environment of an injectable cement with oncotherapeutic potential--consisting of a glass powder of SiO2 (35.6%), CaO (42.4%), P2O5 (17%), Na2O (5%) and 30% of its weight of Fe3O4 dissolved in (NH4)2HPO4 plus NH4H2PO4--was evaluated referring to the release of silicon and iron. The experimental model was the rat, and organs (liver, kidney, spleen, lung, heart, and brain) of the implanted and control animals were collected for quantification of these elements by electrothermal atomization atomic absorption spectrometry methods. In most of the analysed organs no significant difference in the contents of silicon and iron between the implanted and the control animals was found.

Topics: Animals; Biocompatible Materials; Ceramics; Hot Temperature; Humans; Iron; Magnetics; Materials Testing; Neoplasms; Prostheses and Implants; Rats; Reproducibility of Results; Silicon; Tissue Extracts

Silicon diode dosimeters have been used routinely for in-vivo dosimetry. Despite their popularity, an appropriate implementation of an in-vivo dosimetry program using diode detectors remains a challenge for clinical physicists. One common approach is to relate the diode readout to the entrance dose, that is, dose to the reference depth of maximum dose such as d(max) for the 10x10 cm(2) field. Various correction factors are needed in order to properly infer the entrance dose from the diode readout, depending on field sizes, target-to-surface distances (TSD), and accessories (such as wedges and compensate filters). In some clinical practices, however, no correction factor is used. In this case, a diode-dosimeter-based in-vivo dosimetry program may not serve the purpose effectively; that is, to provide an overall check of the dosimetry procedure. In this paper, we provide a formula to relate the diode readout to the entrance dose. Correction factors for TSD, field size, and wedges used in this formula are also clearly defined. Two types of commercial diode detectors, ISORAD (n-type) and the newly available QED (p-type) (Sun Nuclear Corporation), are studied. We compared correction factors for TSDs, field sizes, and wedges. Our results are consistent with the theory of radiation damage of silicon diodes. Radiation damage has been shown to be more serious for n-type than for p-type detectors. In general, both types of diode dosimeters require correction factors depending on beam energy, TSD, field size, and wedge. The magnitudes of corrections for QED (p-type) diodes are smaller than ISORAD detectors.

Topics: Humans; Models, Theoretical; Neoplasms; Radiation Monitoring; Radiotherapy Dosage; Silicon

A plethora of data has been used to condemn and defend the role of silicone and its association with "adjuvant disease." In the ongoing attempt to enhance our knowledge, we have chosen to identify tissue silicon levels (n = 15) in capsules that form around chemotherapeutic port-a-catheter devices, which consist of a metal dome encapsuled by silicone. We have compared these levels with previously established silicon levels in augmented breast capsules, distant tissue sites in these same augmented women, and nonaugmented cadaveric tissues from various geographic locations in the United States. All specimens were harvested by a "no touch" technique, not formalin fixed, frozen, and shipped to an independent toxicology laboratory for analysis. Inductively coupled plasma atomic emission spectroscopy was employed to obtain the tissue silicon measurements. Results demonstrated silicon values ranging from nondetectable in 9 patients to as high as 41 micrograms/gm. These values fell in between our cadaveric (0.5 to 6.8 micrograms/gm) and augmented tissue silicon levels (18 to 8700 micrograms/gm). Although the sample size is small and the power of statistical analysis is low, there was no correlation between the patient's silicon level and age, type of cancer, type of chemotherapeutic agent, radiation therapy, or length of time the port-a-catheters were in place. Although detectable levels of silicon identified around port-a-catheter devices were higher than expected, it is impossible to make any conclusions about these levels and the role of a potential collagen-vascular disease. What we have shown, however, is that silicone breast implants may not be the only medical device that can elevate tissue silicon levels. Our data seem to suggest that there may be a progression of measurable tissue silicon levels based on the amount of environmental or device-related silicon exposure a person has had at a particular time in his or her life. It is our belief that as we identify these tissue silicon levels, they will serve as a baseline and reference for further scientific studies.

Topics: Adolescent; Adult; Age Factors; Alloys; Breast; Breast Implants; Cadaver; Catheters, Indwelling; Child; Child, Preschool; Collagen Diseases; Connective Tissue; Equipment Design; Female; Humans; Infusion Pumps, Implantable; Male; Middle Aged; Neoplasms; Sample Size; Silicon; Silicones; Spectrum Analysis; Time Factors; Tissue Distribution; Vascular Diseases

The continuing development of probes for use with beta (positron and electron) emitting radionuclides may result in more complete excision of tracer-avid tumors. Perhaps one of the most promising radiopharmaceuticals for this task is 18F-labeled-Fluoro-2-Deoxy-D-Glucose (FDG). This positron-emitting agent has been demonstrated to be avidly and rapidly absorbed by many human cancers. We have investigated the use of ion-implanted-silicon detectors in intraoperative positron-sensitive surgical probes for use with FDG. These detectors possess very high positron detection efficiency, while the efficiency for 511 keV photon detection is low. The spatial resolution, as well as positron and annihilation photon detection sensitivity, of an ion-implanted-silicon detector used with 18F was measured at several energy thresholds. In addition, the ability of the device to detect the presence of relatively small amounts of FDG during surgery was evaluated by simulating a surgical field in which some tumor was left intact following lesion excision. The performance of the ion-implanted-silicon detector was compared to the operating characteristics of a positron-sensitive surgical probe which utilizes plastic scintillator. In all areas of performance the ion-implanted-silicon detector proved superior to the plastic scintillator-based probe. At an energy threshold of 14 keV positron sensitivity measured for the ion-implanted-silicon detector was 101.3 cps/kBq, photon sensitivity was 7.4 cps/kBq. In addition, spatial resolution was found to be relatively unaffected by the presence of distant sources of annihilation photon flux. Finally, the detector was demonstrated to be able to localize small amounts of FDG in a simulated tumor bed; indicating that this device has promise as a probe to aid in FDG-guided surgery.

Topics: Beta Particles; Deoxyglucose; Electrons; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Humans; Intraoperative Period; Neoplasms; Radiation Dosage; Radiometry; Radionuclide Imaging; Sensitivity and Specificity; Silicon

Results are presented of a cohort study on the incidence of cancers and crude death rates in ferrochromium and ferrosilicon workers. The whole cohort was observed from 1 January 1953 to 31 December 1985. Two sets of results are presented; one restricted to workers first employed before 1960 and one to workers first employed before 1965. The latter cohort consists of 1235 workers. The total mortality in the whole cohort was low (SMR = 81) as was the overall incidence of cancers (SIR = 84). There was an overall deficit of deaths and cases of cancer in the ferrosilicon group. An excess of lung cancer (SIR = 154) and cancer of the prostate (SIR = 151) was observed in the ferrochromium workers employed before 1965. Cancer of the kidney was also in excess (SIR = 273) in the ferrochromium group, with a mean "latency time" of 39 years. Two cases of malignant melanomas had occurred versus 0.19 expected in a small subgroup of workers in electrical shops and an electric power station.

Topics: Chromium; Female; Humans; Incidence; Iron; Male; Metallurgy; Neoplasms; Norway; Occupational Diseases; Rectal Neoplasms; Silicon; Time Factors

Ferromagnetic alloys, used in the form of "thermoseeds" for surgical implantation, have been developed and used to induce localized hyperthermia in cancerous growths. Alloys of nickel with approx. 4 wt.% Si were chosen for this study because they have Curie temperatures in the desired range of 45-60 degrees C. The thermoseeds were prepared by using either a special casting technique or casting and swaging followed by homogenization. The effects of these different processing schedules on the magnetic behavior of these alloys are discussed. In particular, the importance of minimizing oxidation during melting and heat treating, and the effects of homogenizing the thermoseeds on the relative permeability at temperatures near the Curie temperature are pointed out. The best processing schedule is casting small ingots while avoiding oxidation, followed by swaging, drawing, and homogenization. Actual induction heating experiments and the results from magnetization tests indicate that Ni-4 wt.% Si alloys prepared in this manner can be used as thermoseeds with predictable Curie temperatures. These thermoseeds can be used to obtain nearly uniform and constant temperatures in tumors with variable blood flows.

Topics: Alloys; Animals; Biocompatible Materials; Electromagnetic Phenomena; Ferric Compounds; Hot Temperature; Humans; Materials Testing; Neoplasms; Nickel; Prostheses and Implants; Silicon

Attapulgite (palygorskite) and sepiolite are fibrous clay minerals used commercially as components in a wide variety of products including oil and grease adsorbents, carriers for pharmaceuticals, cosmetics, and pesticides. They are also components of drilling muds and animal litter and they are used as paint thickeners. The current annual worldwide production of these minerals exceeds one million tons. Although fibrous in nature, the fibre length may vary greatly depending on the location of the geological deposits. American attapulgite is short (0.1-2.5 micron in length, median of 0.4 micron) but palygorskite from other parts of the world is much longer (30% longer than 5 micron). Several samples of these materials have been submitted to scanning transmission electron microscopy (STEM). This paper reports the results of microscopic evaluations and makes a comparison with the data from experimental carcinogenicity studies and it is concluded that fibre length is a most important carcinogenic property.

Topics: Environmental Exposure; Humans; Magnesium; Magnesium Compounds; Magnesium Silicates; Microscopy, Electron, Scanning; Minerals; Neoplasms; Risk; Silicon; Silicon Compounds

Earlier epidemiological studies have shown that exposure to aluminium oxide and silicon carbide might carry with it an increased risk of lymphomas, stomach cancer, and non-malignant respiratory disease. To elucidate further this possible hazard, the cancer morbidity and the total mortality pattern was studied among 521 men manufacturing abrasive materials who had been exposed to aluminium oxide, silicon carbide, and formaldehyde. Total dust levels were in the range of 0.1-1.0 mg/m3. The cohort was followed up from 1958 until December 1983. No significant increase was found in total mortality, cancer mortality, or incidence of non-malignant respiratory diseases.

Topics: Aluminum Oxide; Carbon; Carbon Compounds, Inorganic; Formaldehyde; Humans; Male; Neoplasms; Occupational Diseases; Silicon; Silicon Compounds; Sweden

The objectives of this Department of Energy sponsored program are (1) to improve existing nuclear techniques, and (2) to develop new techniques for the analysis and solution of both medical problems and those associated with environmental pollution. Measurement facilities developed, to date, include a unique whole body counter, (WBC); a total body neutron activation facility (TBNAA); and a partial body activation facility (PBNAA). A variation of the prompt gamma neutron activation technique for measuring total body nitrogen has been developed to study body composition of cancer patients and the effect of nutritional regimens on the composition. These new techniques provide data in numerous clinical studies not previously amenable to investigation. The development and perfection of these techniques provide unique applications of radiation and radioisotopes to the early diagnosis of certain diseases and the evaluation of therapeutic programs. The PBNAA technique has been developed and calibrated for in vivo measurement of metals. Development has gone forward on prompt gamma neutron activation for the measurement of cadmium, x-ray fluorescence (XRF) for measurement of lead, and nuclear resonance scattering (NRS) for measurement of iron. Other techniques are being investigated for in vivo measurement of metals such as silicon and beryllium. Cardinal to all toxicological studies of Cd and other metal pollutants is an accurate and sensitive noninvasive technique for measuring organ burdens. In keeping with the mission of Brookhaven, these facilities have been made available to qualified scientists and members of the medical community throughout the world.

Topics: Adult; Aged; Body Composition; Brain Chemistry; Cadmium; Calcium; Elements; Humans; Iron; Lead; Lung; Magnetic Resonance Spectroscopy; Middle Aged; Neoplasms; Neutron Activation Analysis; Nitrogen; Scattering, Radiation; Silicon; Spectrometry, X-Ray Emission

Topics: Elementary Particles; Energy Transfer; Humans; Male; Mouth Neoplasms; Nasopharyngeal Neoplasms; Neoplasms; Prostatic Neoplasms; Radiometry; Radiotherapy Dosage; Silicon

Topics: Aged; Chromium; Chromium Alloys; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Norway; Occupational Diseases; Prostatic Neoplasms; Silicon; Silicon Compounds

Topics: Animals; Guinea Pigs; Hemiterpenes; Latex; Neoplasms; Neoplasms, Experimental; Plastics; Rabbits; Research; Rubber; Sarcoma; Sarcoma, Experimental; Silicon; Surgery, Plastic

Topics: Humans; Neoplasms; Silicon

Topics: Neoplasms; Silicic Acid; Silicon

Topics: Humans; Inorganic Chemicals; Neoplasms; Silicon; Silicon Compounds