Polymersomes with Rapid K⁺-Triggered Drug-Release Behaviors

A novel type of smart polymersomes with rapid K + -triggered drug-release properties is developed in this work. Block copolymers with biocompatible poly(ethylene glycol) (PEG) as the hydrophilic block and poly( N -isopropylacrylamide- co -benzo-18-crown-6-acrylamide) (PNB) copolymer as the K + -responsive block are successfully synthesized. Because of the presence of 18-crown-6 units, the PEG- b -PNB block copolymers exhibit excellent K + -dependent phase-transition behaviors, which show a hydrophilic–hydrophobic state in simulated extracellular fluid and present a hydrophilic–hydrophilic state in simulated intracellular fluid. Polymersomes with regular spherical shape and good monodispersity are prepared by the self-assembly of the PEG- b -PNB block copolymers. Both hydrophilic fluorescein isothiocyanate–dextran and hydrophobic doxorubicin are selected as model drugs and are successfully encapsulated into the PEG- b -PNB polymersomes. After being placed in a simulated intracellular fluid with high K + concentration, the PEG- b -PNB polymersomes immediately disassemble accompanied by the rapid and complete release of drugs. Such K + -responsive polymersomes with the desired drug-release properties provide a novel strategy for advanced intracellular drug delivery and release, which can enhance the safety and efficacy of cancer therapy.