Supramolecular cisplatin-vorinostat nanodrug for overcoming drug resistance in cancer synergistic therapy

Abstract

Cisplatin is a widely used anticancer drug in clinic. However, it may induce drug resistance after a course of treatment and it is difficult to accumulate at tumor site selectively, which result in clinic failure and side effects. We successfully bound cisplatin with vorinostat (a FDA-approved histone deacetylase inhibitor) to form a supramolecular conjugate, which can further self-assemble into nanoparticles. The nanodrug can retain in blood stream for a long time, accumulate in tumor site and hydrolyze to release the two drugs for synergistic therapy. In vivo experiments highlighted the great advantage of the supramolecular nanodrug, because it ensured the two drugs reaching cancer tissue simutaneously. Free cisplatin or cisplatin/vorinostat mixture had negligible or limited effects on A549/DR tumor growth. On the contrary, the tumor inhibitory rate approached 99% with little systemic toxicity if the dose of cisplatin-vorinostat nanodrug reached 10mg/kg body weight, thus suggesting this supramolecular nanodrug as a promising treatment of drug resistance cancer.