The aim of this study was the synthesis of a platform with an optimum physicochemical property and photocatalytic activity for delivery of a standard chemotherapy drug, doxorubicin (Dox). The mesoporous rod-shaped zinc oxide/hydroxyapatite (ZnO@HAP) heterostructures were successfully fabricated and characterized by XRD, FT-IR, FE-SEM, and EDX, and then the nanocomposites with well-defined properties were selected as a nanocarrier for the delivery of Dox. The drug delivery system was decorated with F127 and folic acid (FA), providing a water-soluble system in aqueous medium and targeting effects against tumor cells, respectively. Afterward, Dox was loaded on the surface of the nanocomposites through a single-emulsion solvent-evaporation method. Drug release assessment revealed that proteases cause the release of Dox under a low pH condition, imitating the intracellular compartments like the lysosomes. Based on the biological studies, Dox&FA.F127.ZnO@HAP exerted the most efficient cytotoxic activity against the tumor cells as it was along with the UVA treating. Moreover, it was found that Dox&FA.F127.ZnO@HAP possesses higher cellular uptake efficiency relative to free Dox, particularly in folate-overexpressed tumor cells through clathrin-mediated endocytic pathway. In addition, co-treatment of the tumor cells with Dox&FA.F127.ZnO@HAP and UVA intensified the production of intracellular ROS and drastically enhanced cellular death with mode of apoptosis.

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