Nanoparticle delivery of a triple-action Pt(iv) prodrug to overcome cisplatin resistance via synergistic effect

Abstract

Cisplatin is the most widely used chemotherapeutic agent due to its efficacy in the treatment of a broad range of cancer types; while the side effects and drug resistance of cisplatin limit its clincial application. Combination therapy, which contains several types of free drugs, exhibits promising potential in clinical practice. Nevertheless, current combination chemotherapy cannot accurately deliver different drug components into a single tumor cell at the same time. Herein, we report a triple-action nanoplatinum drug based on artesunate and cantharidin to overcome the influence of pharmacokinetics and distribution variation in different drugs. The results show that the triple action nanoplatinum drug enhances ROS generation, leads to DNA damage, and inhibits DNA repair. Therefore, a high-efficiency killing effect is achieved with a triple-action platinum drug in a single tumor cell.