Coordinative Double Hydrophilic All-Polyether Micelles for pH-Responsive Delivery of Cisplatin

Despite its widespread use in the treatment of numerous cancers, the use of cisplatin still raises concerns about its high toxicity and limited selectivity. Consequently, the necessity arises for the development of an effective drug delivery system. Here, we present an effective approach that introduces a double hydrophilic block copolyether for the controlled delivery of cisplatin. Specifically, poly(ethylene glycol)-block-poly(glycidoxy acetic acid) (mPEG-b-PGA) was synthesized via anionic ring-opening polymerization using the oxazoline-based epoxide monomer 4,4-dimethyl-2-oxazoline glycidyl ether, followed by subsequent acidic deprotection. The coordinative metal-ligand interaction between cisplatin and the carboxylate group within the PGA block facilitated the formation of micelles from the double hydrophilic mPEG-b-PGA copolyether. Cisplatin-loaded polymeric micelles had a high loading capacity, controlled pH-responsive release kinetics, and high cell viability. Furthermore, in vitro biological assays revealed cellular apoptosis induced by the cisplatin-loaded micelles. This study thus successfully demonstrates the potential use of double hydrophilic block copolyethers as a versatile platform for biomedical applications.