Biological Effects Of Titania Nanoparticles And Their Application As Anti-cancer Drug Vehicle In Breast Cancer Therapy

With the fast development of nanotechnology, the research of application and bio-safty of nanoparticles is thereupon springing up. Nanoscale titanium dioxide or titania (TiO₂) is widely used in diverse fields of coating, cosmetics, food additive, etc., because of its inherent physical and chemical properties. The possibility of application of TiO₂ nanotubes (TiO₂-NTs) as the drug deliver system in cancer therapy was explored. This study focuses on the cytotoxicity, internerlization, translocation, and the mechanism of TiO₂ in neural stem cells (NSCs). The main research results are as follows:1) TiO₂ NTs showed no cytotoxicity and nor effects to the cell cycle and cell apoptosis in the low concentration below 50 ppm. TiO₂ -NTs possesses excellent biocompatibility.2) Titania nanoparticles (TiO₂-NPs) and titania nanotubes (TiO₂-NTs) easily pass through the cell membrane by endocytosis. At the 24 h co-incubation time, the TiO₂ localized into cells mainly via endocytosis and then inside endosome vesicles. With prolonging time, TiO₂-NPs were biotransformed by some kinds of lysoenzyme in endosome. When the co-incubation time was prolonged to 48 h, TiO₂-NTs penetrated into the cell nucleus.3) We found that DOX could load on the TiO₂-NTs, the best load concertration and time of DOX was 0.7 mg/ml and 24 h. Its encapsulation ratio was up to 72% and loading rate 40%. DOX was very stable at the condition of pH=7. When at pH=3, the release rate greatly increased. The final release rate was 80%.4) BABL/C mices bearing breast cancer were used to study the DOX loaded TiO₂-NTs as a drug delivery vehicle (TiO₂-NTs-DOX) in the cancer therapy. It was unexpectedly demonstrated that TiO₂-NTs per se had high inhibitory effect to breast cancer and there was obvious dose dependence. The reduction of tumor volume was 66.27% at the dose of 125 mg/kg. The reduction of tumor volume of TiO₂-NTs-DOX is lower than TiO₂-NTs. However, the inhibition mechanism of TiO₂-NTs needs further study. We suggested that the abundant hydroxyl groups on the TiO₂-NTs surface may provoke the mice immune system, hence enhance immunity and improve the functions against cancer.These results provide some fundamental data for the application of TiO₂-NTs as a drug delivery vehicle in the cancer therapy.