clay and Lung-Neoplasms

Cancer recurrence and metastasis are worldwide challenges but current bimodular strategies such as combined radiotherapy and chemotherapy (CTX), and photothermal therapy (PTT) and immunotherapy have succeeded only in some limited cases. Thus in the present study, a multifunctional nanomedicine has been rationally designed via elegantly integrating three FDA-approved therapeutics, that is, indocyanine green (for PTT), doxorubicin (for CTX), and CpG (for immunotherapy) into the structure of layered double hydroxide (LDH) nanoparticles, aiming to completely prevent the recurrence and metastasis of invasive breast cancer. This multifunctional hybrid nanomedicine has been demonstrated to eliminate the primary tumor and efficiently prevent tumor recurrence and lung metastasis through combined PTT/CTX and induction of specific and strong immune responses mediated by the hybrid nanomedicine in a 4T1 breast cancer mouse model. Furthermore, the promoted in situ immunity has significantly inhibited the growth of reinoculated distant tumors. Altogether, our multifunctional LDH-based nanomedicine has showed an excellent efficacy in invasive cancer treatment using much lower doses of three FDA-approved therapeutics, providing a preclinical/clinical alternative to cost-effectively treat invasive breast cancer.

Topics: Animals; Breast Neoplasms; Clay; Female; Humans; Lung Neoplasms; MCF-7 Cells; Mice; Mice, Inbred BALB C; Nanomedicine; Nanoparticles; Neoplasm Invasiveness; Neoplasm Metastasis; Xenograft Model Antitumor Assays

Fabrication of stimuli-triggered drug delivery vehicle s is an important milestone in treating cancer. Here we demonstrate the selective anticancer drug delivery into human cells with biocompatible 50-nm diameter halloysite nanotube carriers. Physically-adsorbed dextrin end stoppers secure the intercellular release of brilliant green. Drug-loaded nanotubes penetrate through the cellular membranes and their uptake efficiency depends on the cells growth rate. Intercellular glycosyl hydrolases-mediated decomposition of the dextrin tube-end stoppers triggers the release of the lumen-loaded brilliant green, which allowed for preferable elimination of human lung carcinoma cells (А549) as compared with hepatoma cells (Hep3b). The enzyme-activated intracellular delivery of brilliant green using dextrin-coated halloysite nanotubes is a promising platform for anticancer treatment.

Topics: Actins; Aluminum Silicates; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Survival; Clay; Dextrins; Drug Carriers; Humans; Liver Neoplasms; Lung Neoplasms; Microscopy, Atomic Force; Microscopy, Electron, Transmission; Mitochondria; Nanotubes; Pharmaceutical Preparations; Quaternary Ammonium Compounds

Circulating tumor cells (CTCs) can be used clinically to treat cancer. As a diagnostic tool, the CTC count can be used to follow disease progression, and as a treatment tool, CTCs can be used to rapidly develop personalized therapeutic strategies. To be effectively used, however, CTCs must be isolated at high purity without inflicting cellular damage.. We designed a microscale flow device with a functionalized surface of E-selectin and antibody molecules against epithelial markers. The device was additionally enhanced with a halloysite nanotube coating. We created model samples in which a known number of labeled cancer cells were suspended in healthy whole blood to determine device capture efficiency. We then isolated and cultured primary CTCs from buffy coat samples of patients diagnosed with metastatic cancer.. Approximately 50% of CTCs were captured from model samples. Samples from 12 metastatic cancer patients and 8 healthy participants were processed in nanotube-coated or smooth devices to isolate CTCs. We isolated 20-704 viable CTCs per 3.75-mL sample, achieving purities of 18%-80% CTCs. The nanotube-coated surface significantly improved capture purities (P = 0.0004). Experiments suggested that this increase in purity was due to suppression of leukocyte spreading.. The device successfully isolates viable CTCs from both blood and buffy coat samples. The approximately 50% capture rate with purities >50% with the nanotube coating demonstrates the functionality of this device in a clinical setting and opens the door for personalized cancer therapies.

Topics: Aluminum Silicates; Antibodies; Antigens, Neoplasm; Antigens, Surface; Blood Buffy Coat; Breast Neoplasms; Cell Adhesion; Cell Adhesion Molecules; Cell Count; Cell Separation; Clay; E-Selectin; Epithelial Cell Adhesion Molecule; Female; Glutamate Carboxypeptidase II; Humans; Leukocytes; Lung Neoplasms; Male; Nanotubes; Neoplasm Metastasis; Neoplastic Cells, Circulating; Ovarian Neoplasms; Polyurethanes; Prostatic Neoplasms

Evaluation of contrast enhancement of pulmonary lesions with ground-glass attenuation (GGA) is difficult with conventional techniques but might be possible using contrast-mapping images (CMIs) obtained by dual-energy computed tomography. To address this issue, a phantom study was conducted, and this technique was then applied to clinical cases.. Phantoms made of agarose gel and those made of hollow resin clay, containing various concentrations of iodine or calcium, were used to simulate soft tissue and GGA, respectively. They were scanned using a dual-energy computed tomographic scanner, and the relationship between iodine concentration and calculated iodine value on CMIs was examined. The influence of calcium was also evaluated. In addition, contrast enhancement of 24 GGA lesions was evaluated on CMIs.. There was a good correlation between iodine value and iodine concentration in the soft-tissue models (r(2) = 0.996). In the GGA models, the former tended to exceed the latter when default parameters for calculating CMIs were used, but this could be corrected by modifying the parameters (r(2) = 0.998). The iodine value increased with calcium concentration in both models. On CMIs, contrast enhancement was visible in 22 adenocarcinomas but not in a pulmonary hemorrhage and an inflammatory change.. Dual-energy computed tomography can evaluate contrast enhancement of GGA lesions.

Topics: Aged; Aged, 80 and over; Aluminum Silicates; Calcium Carbonate; Clay; Contrast Media; Female; Humans; Iodates; Iopamidol; Linear Models; Lung Neoplasms; Male; Middle Aged; Phantoms, Imaging; Potassium Compounds; Sepharose; Tomography, X-Ray Computed

Many researches have shown that anionic clays can be used as delivery carriers for drug or gene molecules due to their efficient cellular uptake in vitro, and enhanced permeability and retention effect in vivo. It is, therefore, highly required to establish a guideline on their potential toxicity for practical applications. The toxicity of anionic clay, layered metal hydroxide nanoparticle, was evaluated in two human lung epithelial cells, carcinoma A549 cells and normal L-132 cells, and compared with that in other human cancer cell lines such as cervical adenocarcinoma cells (HeLa) and osteosarcoma cells (HOS). The present nanoparticles showed little cytotoxic effects on the proliferation and viability of four cell lines tested at the concentrations used (<250 microg/ml) within 48 h. However, exposing cancer cells to high concentrations (250-500 microg/ml) for 72 h resulted in an inflammatory response with oxidative stress and membrane damage, which varied with the cell type (A549>HOS>HeLa). On the other hand, the toxicity mechanism seems to be different from that of other inorganic nanoparticles frequently studied for biological and medicinal applications such as iron oxide, silica, and single walled carbon nanotubes. Iron oxide caused cell death associated with membrane damage, while single walled carbon nanotube induced oxidative stress followed by apoptosis. Silica triggered an inflammation response without causing considerable cell death for both cancer cells and normal cells, whereas layered metal hydroxide nanoparticle did not show any cytotoxic effects on normal L-132 cells in terms of inflammation response, oxidative stress, and membrane damage at the concentration of less than 250 microg/ml. It is , therefore, highly expected that the present nanoparticle can be used as a efficient vehicle for drug delivery and cancer cell targeting as well.

Topics: Aluminum Silicates; Apoptosis; Cell Line; Cell Proliferation; Cell Survival; Clay; Drug Delivery Systems; Epithelial Cells; Humans; Interleukin-8; L-Lactate Dehydrogenase; Lung Neoplasms; Microscopy, Electron, Scanning; Nanoparticles; Reactive Oxygen Species