Constructing pH-responsive poly(trimethylene carbonate) (PTMC)-based polymersomes functionalized with cell-penetrating guanidines

Abstract

pH-responsive polymer vesicles (polymersomes) hold great potential in the field of drug delivery. However, the use of pH-responsive polymersome systems as drug vehicles generally suffers from low cellular uptake efficiency. In this work, we constructed guanidinylated pH-responsive polymersomes comprising poly(trimethylene carbonate) (PTMC) based polymers with pedants of pH-responsive moieties. The polymersomes are characterized by the pH-induced disassembly, which was utilized for controlled drug release. We find that coupling of guanidine groups with the surface of polymersomes can significantly improve the internalization of polymersomes within cancer cells due to the strong interactions between guanidines and cell surface membranes. Additionally, the in vitro studies demonstrate that drug-loaded guanidine-functionalized polymersomes are capable of inducing enhanced cancer cell death as compared to unfunctionalized polymersomes. Hence, the synergistic combination of pH-responsive property and cell-penetrating feature in polymersome particles offers a new strategy for constructing advanced pH-responsive polymeric nanocarriers.