Co-delivery of oxaliplatin and demethylcantharidin via a polymer-drug conjugate

Abstract

A Pt (IV) complex which combined the bioactivities of both oxaliplatin and demethylcantharidin (DMC) is synthesized and delivered by a polymer-drug conjugate for combination chemotherapy. Oxaliplatin is released from the polymer-drug conjugate within cancer cell by reduction to attack nuclear DNA, while a dose of DMC is also hydrolyzed subsequently to block DNA damage-induced defense mechanisms by serine/threonine phosphatase 2A (PP2A) inhibition. In vitro evaluation shows that the polymer-drug conjugate with dual modes of action upon cancer cells displays higher cytotoxicity against SKOV-3 cells than that of free drugs. This enhanced cytotoxicity is attributed to the synergistic effect between oxaliplatin and DMC, as well as the effective intracellular internalization of the micelles observed by confocal laser scanning microscopy (CLSM) imaging.

Keywords: PP2A inhibition; co-delivery; combination chemotherapy; oxaliplatin; polymer-drug conjugate.