Construction of poly(trimethylene carbonate)-based polymersomes for reactive oxygen species (ROS)-induced nitric oxide (NO) release.

L-Arginine (L-Arg), an endogenous precursor for nitric oxide (NO) production, is attractive for constructing responsive NO delivery systems based on natural precursor molecules. However, current L-Arg delivery systems still face limitations in carrier design, mild preparation, and systematic verification of NO release. Herein, amphiphilic block copolymers, poly(ethylene glycol)-block-poly[(ε-caprolactone)-gradient-(trimethylene carbonate)] (PEG-b-P[(CL)-g-(TMC)]), were synthesized by ring-opening polymerization and assembled into L-Arg-loaded polymersomes via direct hydration. Under reactive oxygen species (ROS) conditions simulated by hydrogen peroxide (H2O2), the polymersomes continuously produced NO, and NO release increased with increasing H2O2 concentration. Overall, this work establishes an L-Arg-loaded polymersome system prepared under mild conditions with quantifiable ROS-responsive NO release and good structural stability, providing a useful platform for NO delivery based on natural precursor molecules.