Targeted delivery of adenosine 5′-triphosphate using chitosan-coated mesoporous hydroxyapatite: A theranostic pH-sensitive nanoplatform with enhanced anti-cancer effect

Abstract

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