Efficacy of Dipeptide-Coated Magnetic Nanoparticles in Lung Cancer Models Under Pulsed Electromagnetic Field.

Lung cancer is the leading cause of cancer deaths and the overall 5-year survival rate is less than 17%. Hyperthermia is an alternative approach for the treatment of lung cancer and is associated with fewer side effects. We employed ironoxide nanoparticles in inducing localized hyperthermia in lung cancer cells using a pulsed electromagnetic field (PEMF). We synthesized, characterized and determined the uptake of dipeptide-coated iron oxide nanoparticles. Further, their ability in inducing localized hyperthermia in PEMF on lung cancer cells was assessed. Results showed nanoparticles are non-cytotoxic and showed enhanced cellular uptake in lung cancer cells. In vivo studies in nude mice lung tumor xenografts confirmed the presence in the tumors. Lung cancer cells pretreated with dipeptide-coated magnetic nanoparticles upon PEMF exposure induced cell death.

Molecular mechanism of anti-cancer activity of phycocyanin in triple-negative breast cancer cells.

BACKGROUND: Triple-negative breast cancers represent an important clinical challenge, as these cancers do not respond to conventional endocrine therapies or other available targeted agents. Phycocyanin (PC), a natural, water soluble and non-toxic molecule is shown to have potent anti-cancer property. METHODS: In this study, we determined the efficacy of PC as an anti-neoplastic agent in vitro on a series of breast cancer cell lines. We studied effects of PC in inducing DNA damage and apoptosis through western blot and qPCR. Also, anti-metastatic and anti-angiogenic properties were studied by classic wound healing and vasculogenic mimicry assays. RESULTS: We found that triple negative MDA-MB-231 cells were most sensitive to PC (IC50 : 5.98 ± 0.95 µM) as compared to other cells. They also showed decreased cell proliferation and reduced colony formation ability upon treatment with PC. Profile of Cell cycle analysis showed that PC caused G1 arrest which could be attributed to decreased mRNA levels of Cyclin E and CDK-2 and increased p21 levels. Mechanistic studies revealed that PC induced apoptosis as evident by increase in percentage of annexin positive cells, increase in γ-H2AX levels, and by changing the Bcl-2/Bax ratio followed by release of cytochrome C and increased Caspase 9 levels. MDA MB 231 cells treated with PC resulted in decreased cell migration and increased cell adhesive property and also showed anti-angiogenic effects. We also observed that PC suppressed cyclooxygenase-2 (COX-2) expression and prostaglandin E(2) production. All these biological effects of phycocyanin on MDA MB 231 cells could be attributed to decreased MAPK signaling pathway. We also observed that PC is non-toxic to non-malignant cells, platelets and RBC's. CONCLUSION: Taken together, these findings demonstrate, for the first time, that PC may be a promising anti-neoplastic agent for treatment of triple negative breast cancers.

Nanomedicine: towards development of patient-friendly drug-delivery systems for oncological applications.

The focus on nanotechnology in cancer treatment and diagnosis has intensified due to the serious side effects caused by anticancer agents as a result of their cytotoxic actions on normal cells. This nonspecific action of chemotherapy has awakened a need for formulations capable of definitive targeting with enhanced tumor-killing. Nanooncology, the application of nanobiotechnology to the management of cancer, is currently the most important area of nanomedicine. Currently several nanomaterial-based drug-delivery systems are in vogue and several others are in various stages of development. Tumor-targeted drug-delivery systems are envisioned as magic bullets for cancer therapy and several groups are working globally for development of robust systems.

Blood compatibility of iron-doped nanosize hydroxyapatite and its drug release.

Nanosize hydroxyapatite (nHAp) doped with varying levels of Fe(3+) (Fe-nHAp of average size 75 nm) was synthesized by hydrothermal and microwave techniques. The samples were characterized for physiochemical properties by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), inductively coupled plasma optical emission spectrometer (ICP-OES), transmission electron microscopy (TEM), vibrating sample magnetometer (VSM), mechanical and dielectric properties. The biological properties like hemocompatibility, antibacterial efficacy, in vitro bioactivity and the cell proliferation of the samples were determined. XRD pattern of the samples were of single phase hydroxyapatite. As the content of Fe(3+) increased, the crystallite size as well as crystallinity decreased along with a morphological change from spherulites to rods. The dielectric constants and Vickers hardness were enhanced on Fe(3+) doping. The VSM studies revealed that the saturation magnetization (M(s)) and retentivity (M(r)) were found to increase for Fe-nHAp. nHAp impregnated with an antibiotic as a new system for drug delivery in the treatment of chronic osteomyelitis was also attempted. The in vitro drug release with an antibiotic amoxicillin and anticancer drug 5-fluorouracil showed sustained release for the lowest concentration of Fe(3+), while with an increase in the content; there was a rapid release of the drug. The hemolytic assay of Fe(3+) doped samples revealed high blood compatibility (<5% hemolysis). The antibacterial activities of the antibiotic impregnated materials were tested against a culture of E. coli, S. epidermidis and S. aureus by agar diffusion test. The in vitro bioactivity test using simulated body fluid (SBF) showed better bone bonding ability by the formation of an apatite layer on the doped samples. The growth of the apatite layer on the samples surface has been confirmed by EDS analysis. The proliferative potential of MG63 cells by MTT assay confirmed the noncytotoxicity of the samples.