Engineering Oxidation-Responsive Polymeric Self-Assembled Nanoreactors for Enhanced Reactive Oxygen Species (ROS) Scavenging.

Enzyme-enabled biocatalysis demonstrates potent reactive oxygen species (ROS) scavenging performance for oxidative stress mitigation. However, the intrinsic stability and catalytic activity of enzymes are highly susceptible to harsh external microenvironments, which severely restricts their potential applications. Herein, we report the rational design of oxidation-responsive polymeric nanoreactors through encapsulating enzymes within self-assembled vesicular architectures, namely, polymersomes. Upon stimulation with ROS, the membrane permeability of the polymersomes is substantially enhanced, thereby triggering the activation of the encapsulated superoxide dismutase (SOD) and catalase (CAT). Specifically, SOD efficiently scavenges superoxide anions (•O2-) while CAT catalyzes the decomposition of H2O2, enabling sequential and synergistic ROS elimination. Both in vitro and in vivo assessments demonstrate that these oxidation-responsive polymersome nanoreactors significantly improve the therapeutic outcomes for osteoarthritis (OA), offering a versatile and biocompatible platform for the treatment of inflammation-related diseases.