The aim of this study is to investigate the effect of different concentrations of adenosine 5′-triphosphate (ATP) as a stabilizing agent on the physicochemical and biological behavior of AgNPs. The results revealed that the size of distribution and dispersion of AgNPs were controlled by changes in the ratio of ATP and AgNO3 in the presence of NaBH4. The data of FT-IR and zeta potential values show that ATP molecules have been coordinated on the surface of nanoparticles through the adenine moiety of ATP. Cellular viability studies in osteosarcoma cells (Saos-2), breast cancer cells (MCF-7 and T47D), and leukemia cells (K562) demonstrated that ATP-capped silver nanoparticles (ATP@AgNPs) possess high antitumor efficacy compared with the naked ones. It was found that the cellular uptake of ATP@AgNPs occurs through P2X7 receptors and clathrin-mediated endocytosis. As the P2X7 receptor is overexpressed on the surface of many tumor cells; ATP on nanoparticle surface plays the role of a targeting molecule. Moreover, it was demonstrated that the cytotoxicity induced by ATP@AgNPs proceeds from the perturbation of intracellular oxidative status, leading to the induction of apoptosis. From these data, ATP, as “dispersant” and “complexant,” improves the physicochemical properties of AgNPs and potentiates their application in cancer therapy.

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