In this Study, a pH-sensitive nanoplatform made up of chitosan (Cs) and mesoporous hydroxyapatite (HAP) was synthesized and employed for delivering of adenosine 5′-triphosphate (ATP). The fabricated system was decorated with folic acid (FA), providing both tumor targeting and imaging. The FA.Cs.ATP@HAP nanoparticles displayed enhanced colloidal stability and controlled drug release. In vitro biological experiments revealed that FA.Cs.ATP@HAP was internalized into the tumor cells with a high efficiency in a time-dependent manner and exhibited strong fluorescence within the cells. Compared with free ATP, the FA.Cs.ATP@HAP nanoparticles exhibited a significant inhibition effect against the proliferation of the tumor cells (Saos-2, T47D, and MCF7) in a dose-dependent manner, while no significant cytotoxic effect was observed in the normal cells (HEK-293), indicating the selective cytotoxicity of the fabricated nanosystem against the tumor cells. Also, the mechanism of action of FA.Cs.ATP@HAP was investigated, and it was found that it induces a high rate of apoptosis in the tumor cells through a decrease in mitochondrial membrane potential and caspase activation. Based on these findings, FA.Cs.ATP@HAP is a novel biomedical material with targeting, imaging, and high anticancer properties against tumor cells, and it could be considered as a promising candidate for cancer therapy.

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