silicon and Colonic-Neoplasms

The inability of traditional chemotherapeutics to reach cancer tissue reduces the treatment efficacy and leads to adverse effects. A multifunctional nanovector was developed consisting of porous silicon, superparamagnetic iron oxide, calcium carbonate, doxorubicin and polyethylene glycol. The particles integrate magnetic properties with the capacity to retain drug molecules inside the pore matrix at neutral pH to facilitate drug delivery to tumor tissues. The MRI applicability and pH controlled drug release were examined in vitro together with in-depth material characterization. The in vivo biodistribution and compound safety were verified using A549 lung cancer bearing mice before proceeding to therapeutic experiments using CT26 cancer implanted mice. Loading doxorubicin into the porous nanoparticle negated the adverse side effects encountered after intravenous administration highlighting the particles' excellent biocompatibility. Furthermore, the multifunctional nanovector induced 77% tumor reduction after intratumoral injection. The anti-tumor effect was comparable with that of free doxorubicin but with significantly alleviated unwanted effects. These results demonstrate that the developed porous silicon-based nanoparticles represent promising multifunctional drug delivery vectors for cancer monitoring and therapy.

Topics: A549 Cells; Animals; Antibiotics, Antineoplastic; Chemistry, Pharmaceutical; Colonic Neoplasms; Delayed-Action Preparations; Doxorubicin; Drug Delivery Systems; Drug Liberation; Excipients; Humans; Lung Neoplasms; Magnetic Resonance Imaging; Male; Mice; Mice, Inbred NOD; Mice, SCID; Nanoparticles; Porosity; Silicon; Tissue Distribution

The bioavailability of pollen bioactive compounds for humans is limited. In this study, our aim was to enhance the health-related benefits of pollen by fermentation with a Kombucha/SCOBY (symbiotic culture of bacteria and yeasts) consortium. We performed the fermentation of pollen suspended from the beginning with SCOBY on sweetened green tea or on Kombucha vinegar, by adding pollen after 20 days of Kombucha fermentation. We analyzed: formation of bioactive compounds (anti-oxidant polyphenols, soluble silicon, hydroxy-acids, short chain fatty acids-SCFA); parameters related to Kombucha fermentation (dynamics of lactic acid bacteria-LAB, formation of organic acids, soluble sugar evolution on Kombucha vinegar); the influence of Kombucha fermentation on pollen morphology and ultrastructure; in vitro cytotoxic and antitumoral effects of the Kombucha fermented pollen. The pollen addition increases LAB proportion in the total number of SCOBY microbial strains. SEM images highlight the adhesion of the SCOBY bacteria to pollen. Ultrastructural analysis reveals the release of the pollen content. The content of bioactive compounds (polyphenols, soluble silicon species and SCFA) is higher in the fermented pollen and the product shows a moderate antitumoral effect on Caco-2 cells. The health benefits of pollen are enhanced by fermentation with a Kombucha consortium.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Antioxidants; Bacterial Adhesion; Caco-2 Cells; Cell Line, Tumor; Colonic Neoplasms; Culture Media; Drug Compounding; Fatty Acids, Volatile; Fermentation; Food Microbiology; Humans; Kombucha Tea; Lactobacillaceae; Mice; Plant Extracts; Pollen; Polyphenols; Silicon; Sugars; Tea; Yeasts

There are uncertainties associated with the prediction of colorectal cancer (CRC) risk from highly energetic heavy ion (HZE) radiation. We undertook a comprehensive assessment of intestinal and colonic tumorigenesis induced after exposure to high linear energy transfer (high-LET) HZE radiation spanning a range of doses and LET in a CRC mouse model and compared the results with the effects of low-LET γ radiation.. Male and female APC(1638N/+) mice (n=20 mice per group) were whole-body exposed to sham-radiation, γ rays, (12)C, (28)Si, or (56)Fe radiation. For the >1 Gy HZE dose, we used γ-ray equitoxic doses calculated using relative biological effectiveness (RBE) determined previously. The mice were euthanized 150 days after irradiation, and intestinal and colon tumor frequency was scored.. The highest number of tumors was observed after (28)Si, followed by (56)Fe and (12)C radiation, and tumorigenesis showed a male preponderance, especially after (28)Si. Analysis showed greater tumorigenesis per unit of radiation (per cGy) at lower doses, suggesting either radiation-induced elimination of target cells or tumorigenesis reaching a saturation point at higher doses. Calculation of RBE for intestinal and colon tumorigenesis showed the highest value with (28)Si, and lower doses showed greater RBE relative to higher doses.. We have demonstrated that the RBE of heavy ion radiation-induced intestinal and colon tumorigenesis is related to ion energy, LET, gender, and peak RBE is observed at an LET of 69 keV/μm. Our study has implications for understanding risk to astronauts undertaking long duration space missions.

Topics: Animals; Carbon; Colonic Neoplasms; Female; Ferrous Compounds; Gamma Rays; Heavy Ion Radiotherapy; Intestinal Neoplasms; Intestine, Small; Linear Energy Transfer; Male; Mice; Mice, Inbred C57BL; Neoplasms, Radiation-Induced; Radiotherapy Dosage; Relative Biological Effectiveness; Sex Factors; Silicon

The novel thiourea-functionalized silicon nanoparticles (SiNPs) have been successfully synthesized using allylamine and sulforaphane, an important anticancer drug, followed by a hydrosilylation reaction on the surface of hydrogen terminated SiNPs. Their physiochemical properties have been investigated by photoluminescence emission, Fourier transform infrared spectroscopy (FTIR) and elemental analysis. The MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay has been employed to evaluate in vitro toxicity in human colorectal adenocarcinoma (Caco-2) cells and human normal colon epithelial (CCD) cells. The results show significant toxicity of thiourea SiNPs after 72 h of incubation in the cancer cell line, and the toxicity is concentration dependent and saturated for concentrations above 100 μg/mL. Confocal microscopy images have demonstrated the internalization of thiourea-functionalized SiNPs inside the cells. Flow cytometry data has confirmed receptor-mediated targeting in cancer cells. This nanocomposite takes advantage of the epidermal growth factor receptor (EGFR) active targeting of the ligand in addition to the photoluminescence properties of SiNPs for bioimaging purposes. The results suggest that this novel nanosystem can be extrapolated for active targeting of the receptors that are overexpressed in cancer cells such as EGFR using the targeting characteristics of thiourea-functionalized SiNPs and therefore encourage further investigation and development of anticancer agents specifically exploiting the EGFR inhibitory activity of such nanoparticles.

Topics: Caco-2 Cells; Colonic Neoplasms; ErbB Receptors; Gene Expression Regulation, Neoplastic; Humans; Nanoparticles; Particle Size; Silicon; Spectroscopy, Fourier Transform Infrared; Surface Properties; Thiourea

Detection of rare metastatic cells within a benign tumor is a key challenge to diagnose the cancerous stage of the patients tested by clinical human biopsy or pap smear samples. We have fabricated and tested a nanograssed silicon based bioelectronic device with the ability of detecting a few human colon invasive cancer cells (SW48) in a mixed cell culture of primary cancerous colon cells (HT29) without any biochemical labels. A discernible impedance change was elicited after the presence of 5% metastatic cells in the whole benign sample. The electric field penetration as well as current flow to metastatic cells is different from benign ones due to their different membrane dielectric parameters. Beta dispersion as one of intrinsic bioelectrical properties of the cell membrane in blocking the stimulating current flow in the range of kHz is the specific parameter involved in our diagnosis approach. It can reflect in-depth information about the dielectric properties and the pathological condition of a cell before and after metastatic transformation. Electrically active doped silicon nanograss structures owing to their superior nanocontacts with cell membrane can detect any slight variations in current being originated from the presence of rare metastatic cells on the surface of the sensing electrode. The experimental results revealed that bare doped silicon microelectrodes are incapable of resolving different grades of attached cells.

Topics: Biosensing Techniques; Cell Line, Tumor; Colon; Colonic Neoplasms; Electric Impedance; Equipment Design; Humans; Nanostructures; Neoplasm Metastasis; Neoplasm Staging; Silicon; Tumor Cells, Cultured

A multifunctional nano-in-micro drug delivery platform is developed by conjugating the porous silicon nanoparticles with mucoadhesive polymers and subsequent encapsulation into a pH-responsive polymer using microfluidics. The multistage platform shows monodisperse size distribution and pH-responsive payload release, and the released nanoparticles are mucoadhesive. Moreover, this platform is capable of simultaneously loading and releasing multidrugs with distinct properties.

Topics: Caco-2 Cells; Cell Proliferation; Colonic Neoplasms; Drug Delivery Systems; HT29 Cells; Humans; Microfluidics; Microscopy, Electron, Scanning; Microtechnology; Nanoparticles; Nanotechnology; Particle Size; Polymers; Porosity; Silicon

In the systematic administration of cancer, cancer markers are normally used to help the therapeutic agents access the cancer cells spontaneously. Therefore, it is essential to functionalize the surface of porous silicon (pSi) for cancer markers to attach well to pSi in systematic administration because most cancer markers does not attach easily to pSi. The thermal oxidation of pSi is adopted most widely as a surface functionalization technique for pSi. This study examined the photothermal properties and cancer cell-killing ability of oxidized pSi (pSiO). The temperature measurement and in vitro cell tests including the annexin V-fluorescein isothiocyanate (FITC) apoptosis assay tests, MTT assay tests, and Trypan blue cell death assay tests were performed to compare the photothermal properties and the cytotoxic effect of pSiO with those of pSi in combination with an 808-nm NIR laser. pSiO showed lower photothermal properties and a lower cell-death rate than bare pSi. On the other hand, the pSiO treatment used in combination with an NIR laser treatment showed a cytotoxic effect high enough to kill a considerable portion of the cancer cells.

Topics: Animals; Apoptosis; Cell Line, Tumor; Colonic Neoplasms; Hot Temperature; Hyperthermia, Induced; Lasers, Semiconductor; Mice; Neoplasms, Experimental; Oxidation-Reduction; Porosity; Silicon

In-vivo animal tests were performed to investigate the feasibility of photothermal therapy based on porous silicon nanoparticles (PSiNPs) in combination with a near-infrared (NIR) laser. The in-vivo animal test results showed that the murine colon carcinoma (CT-26) tumors were completely resorbed with minimal damage to surrounding healthy tissue within 5 days after PSiNPs and NIR laser treatments. In contrast, tumors in the groups treated only with PSiNPs or NIR and a control group continued to grow until the mice died. All of the mice treated with both PSiNPs and NIR remained healthy and free of tumors even 90 days after the treatment. In-vivo fluorescence imaging and the urine and feces tests revealed that PSiNPs injected intratumorally into mice were cleared mainly through the urine. The in-vivo animal test results suggest that thermotherapy based on porous silicon in combination with NIR laser irradiation can efficiently destroy cancer cells selectively without damaging the surrounding healthy cells.

Topics: Animals; Cell Line, Tumor; Colonic Neoplasms; Fluorescence; Hyperthermia, Induced; Injections, Intralesional; Laser Therapy; Male; Mice; Mice, Inbred BALB C; Nanoparticles; Neoplasms, Experimental; Particle Size; Polyethylene Glycols; Porosity; Silicon; Solutions; Xenograft Model Antitumor Assays

The following study examines the feasibility of nanoshell-assisted photo-thermal therapy (NAPT). This technique takes advantage of the strong near infrared (NIR) absorption of nanoshells, a new class of gold nanoparticles with tunable optical absorptivities that can undergo passive extravasation from the abnormal tumor vasculature due to their nanoscale size. Tumors were grown in immune-competent mice by subcutaneous injection of murine colon carcinoma cells (CT26.WT). Polyethylene glycol (PEG) coated nanoshells (approximately 130 nm diameter) with peak optical absorption in the NIR were intravenously injected and allowed to circulate for 6 h. Tumors were then illuminated with a diode laser (808 nm, 4 W/cm2, 3 min). All such treated tumors abated and treated mice appeared healthy and tumor free >90 days later. Control animals and additional sham-treatment animals (laser treatment without nanoshell injection) were euthanized when tumors grew to a predetermined size, which occurred 6-19 days post-treatment. This simple, non-invasive procedure shows great promise as a technique for selective photo-thermal tumor ablation.

Topics: Animals; Colonic Neoplasms; Feasibility Studies; Female; Gold; Hyperthermia, Induced; Infrared Rays; Lasers; Mice; Mice, Inbred BALB C; Mice, SCID; Microspheres; Phototherapy; Polyethylene Glycols; Silicon; Survival Rate; Temperature

Dietary fibers might lower the risk of colorectal cancer, maybe because of their bulking effect. We tested the protection afforded by an inert bulk against carcinogenesis. Thirty rats received an azoxymethane injection and were allocated to a control diet, or to a diet supplemented with 10% carborundum. After 100 days the colons were scored for aberrant crypt foci. Compared to controls, the fecal weight was doubled in carborundum-fed rats (P < 0.001), but the aberrant crypt foci multiplicity was not changed (P = 0.92). The results do not support the hypothesis that intestinal dilution by an inert bulk can protect against colon cancer.

Topics: Alkaline Phosphatase; Animals; Bile Acids and Salts; Carbon; Carbon Compounds, Inorganic; Colonic Neoplasms; Dietary Fiber; Feces; Female; Intestinal Mucosa; Precancerous Conditions; Rats; Rats, Inbred F344; Silicon; Silicon Compounds

Self-expanding metallic stents were inserted into the ureters of two female patients (29 and 46 years old) with malignant ureteric stenosis, in the first patient caused by metastases of a malignant melanoma, in the second by retroperitoneal lymph-node metastases from a colon carcinoma. In the first patient the stent was introduced antegrade into the left ureter via a nephrostomy after balloon dilatation of the stenotic segment. She was subsequently without symptoms, but six weeks later the ureter got kinked just above the bladder due to continued tumour growth against the stent. After insertion of a silicon splint she had no further symptoms referrable to the kidneys until she died two months later. In the other patient in whom both ureters were obstructed they could not be catheterized percutaneously. Stents were, therefore, introduced transurethrally after previous balloon dilatation of the stenoses. Obstruction occurred in the right ureter three days after the procedure due to mucosal oedema, but it was controlled by anti-inflammatory drugs. Hydronephrosis developed again six months later, caused by circumscribed incrustations in parts of the the stent not covered by mucosa. Silicon splints were placed bilaterally and the patient has so far been free of symptoms for two months.

Topics: Adult; Catheterization; Colonic Neoplasms; Constriction, Pathologic; Female; Humans; Hydronephrosis; Lymphatic Metastasis; Melanoma; Metals; Middle Aged; Prostheses and Implants; Silicon; Stents; Ureteral Neoplasms; Ureteral Obstruction