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Nanoparticles are the new entities that can greatly limit the various side effects of systemic chemotherapy, and that coupled with a targeting moiety enables site-specific delivery of drugs. Folate receptors are overexpressed in retinoblastoma cells, thus these can specifically uptake the drug-loaded nanoparticles, thereby increasing the cytotoxicity at the tumor site. In our work, doxorubicin-loaded chitosan nanoparticles was prepared and then conjugated to folic acid. The conjugation efficiency was characterized by nuclear magnetic resonance and Fourier transform infrared spectroscopy. Thereafter, the efficacy of FA-conjugated DOX-CNPs on retinoblastoma cells (Y-79) was analyzed by MTT assay which demonstrated superior cytotoxic effects as compared to unconjugated DOX-CNPs and native DOX. This may be due to enhanced intracellular uptake of DOX-CNPs-FA (30%) than that of DOX-CNPs (13.24%) and native DOX (5.01%), resulting from the high affinity of FA for folate receptors. Finally, the mechanism of doxorubicin-mediated apoptosis in retinoblastoma cell line (Y-79) was investigated which demonstrated that the mitochondrial pathway is activated and that the FA-conjugated DOX-CNPs are most effective and causes enhanced release of cytochrome c as well as the activation of downstream caspases to assist in apoptosis. Thus, the FA-targeted NPs were proved to possess sustainable, controlled, and targeted delivery of anticancer drugs with DOX as a model drug, which may provide a drug delivery system of precise control and targeting effect for the treatment of retinoblastoma.

cancer nanotechnology

Evaluation of cytotoxicity and mechanism of apoptosis of doxorubicin using folate-decorated chitosan nanoparticles for targeted delivery to retinoblastoma