Engineering Amphiphilic Platinum(IV) Prodrugs for Treating Drug Resistant Ovarian Cancer

Abstract

The platinum(IV) prodrug approach is a promising method to develop a replacement for classic platinum-based chemotherapy. The mitochondria-damaging Pt(IV) prodrugs have proven effective against drug-resistant ovarian cancer cells and cancer stem cells, which represent long-standing issues in classic platinum chemotherapy. In this work, we present a comprehensive study on engineering novel amphiphilic Pt(IV) prodrugs as mitochondria-damaging agents. The key findings in this study include: 1). Hydrophobicity of the head group of such prodrugs dictates their cell entry and cytotoxicity; 2). Amphiphilic Pt(IV) prodrugs exhibits superior therapeutic effects compared to cisplatin and overcomes drug resistance in ovarian cancer; 3). Amphiphilic Pt(IV) prodrugs trigger mitochondrial damage.