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@Fe2O3 nanocomposite was fabricated and used as a platform for drug delivery. ZnO@Fe2O3 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@Fe2O3) was characterized by FT-IR, TGA, zeta potential, and UV-Visible spectroscopy. F-P-M-ZnO@Fe2O3 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@Fe2O3 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@Fe2O3 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@Fe2O3 did not affect normal cells, indicating the selective cytotoxic effect of fabricated nanosystem. From these data, F-P-M-ZnO@Fe2O3 is a dual-responsive nanoplatform which could be considered as an appropriate candidate for targeted chemo-phototherapy in cancer.

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