Fabrication of poly(ethylene glycol)-coated mesoporous nanocomposite ZnO@FeO for methotrexate delivery: An integrated nanoplatform for dual-mode cancer therapy.

Although chemotherapy is an effective strategy for treatment of tumor cells, the non-specific distribution of chemotherapy drugs and their poor aqueous solubility result in impaired treatment and cause serious side effects in patients. In this study, mesoporous ZnO@FeO nanocomposite was fabricated and used as a platform for drug delivery. ZnO@FeO nanocomposite showed a high capacity for the adsorption of chemotherapy drug, methotrexate (MTX). Drug-loaded nanoparticle was coated with poly(ethylene glycol) (PEG), leading to the enhanced colloidal stability and good cytocompatibility. In order to improve tumor selective targeting of PEG-coated nanoparticles, it was also decorated with folic acid. Fabricated drug delivery system (F-P-M-ZnO@FeO) was characterized by FT-IR, TGA, zeta potential, and UV-Visible spectroscopy. F-P-M-ZnO@FeO nanoparticles showed spatio-temporal drug release which was precisely controlled by pH and UVA light. In vitro biological studies on breast cancer cell lines (MCF-7 and T47D cells) revealed that F-P-M-ZnO@FeO nanoparticles can be internalized by clathrin-mediated endocytosis in energy-dependent and folate receptor-dependent manner. Cytotoxicity experiments showed that the treatment of tumor cells with both F-P-M-ZnO@FeO nanoparticle and UV irradiation causes better synergistic effect in inducing cellular apoptosis than the free drug and UV irradiation alone. Induction of apoptosis occurred following the mitochondrial membrane disruption and caspase activation. Moreover, F-P-M-ZnO@FeO did not affect normal cells, indicating the selective cytotoxic effect of fabricated nanosystem. From these data, F-P-M-ZnO@FeO is a dual-responsive nanoplatform which could be considered as an appropriate candidate for targeted chemo-phototherapy in cancer.