Sensitizing nanoparticle based platinum(IV) drugs by curcumin for better chemotherapy

A polymer-cisplatin(IV) conjugate was prepared by attaching Pt(IV)-COOH to a biodegradable amphiphilic block copolymer containing pendant OH groups. The conjugate can assemble into micelles (M(Pt)) with a mean diameter of ca. 169   nm. Further, curcumin (CM) was used to sensitize platinum drug based nanoparticles to overcome cisplatin resistance and enhance antitumor efficacy. In vitro studies showed that M(Pt)/CM combinations had great synergistic effect both on cisplatin sensitive and cisplatin resistant cell lines (A2780 and A2780DDP). In vivo studies showed that M(Pt)/CM had a much lower systemic toxicity and an enhanced antitumor efficacy compared to cisplatin alone or the corresponding cisplatin/CM combinations. Therefore, polymer-cisplatin(IV) conjugate with small molecules that serve as a non-cytotoxic or minimally cytotoxic sensitizer or enhancer provide a promising strategy, which may have potential clinical implications in the near future.