Folic acid-tagged titanium dioxide nanoparticles for enhanced anticancer effect in osteosarcoma cells

Abstract

In this study, folic acid surface modified-Titanium dioxide nanoparticles (FA-TiNP) were prepared as a suitable alternative to conventional chemotherapeutic agents to treat human osteosarcoma. The particle size of TiNP increased marked after polymer assembly on the nanoparticles (NP) surface with a spherical morphology. FA-TiNP exhibited a superior anticancer effect in osteosarcoma cancer cells compared to that of bare TiNP. The reason might due to the specific interaction of FA with the folate receptor which is overexpressed in the cancer cells. Especially, FA-TiNP treated cells exhibited chromatin condensation, cell shrinkage and membrane blebbing. FA-TiNP showed significantly higher cancer cell apoptosis with nearly 38% of cells in apoptosis chamber (early and late) compared to only ~16% for TiNP. The higher proportion of Annexin V positive cells for FA-TiNP treated group was mainly attributed to the higher intracellular uptake of the TiO2. Importantly, FA-TiNP increased the sub-G0 population to ~25% indicating its superior anticancer effect. The results clearly indicated that FA-TiNP induced greater reactive oxygen species (ROS) generation that resulted in higher sub-G0 cell population with higher cell apoptosis. FA-TiNP showed a remarkably higher expression of cytochrome C (Cyt C) with a marked increase in the expression of cleaved caspase-3 and PARP. Overall, results suggest that surface modification of TiNP with a specific targeting moiety could enhance the chances of having successful therapies for cancer diseases.