Reactive oxygen species switcher via MnO2-coated Prussian blue loaded hyaluronic acid methacrylate hydrogel microspheres for local anti-tumor treatment

ROS-induced therapy can eradicate breast tumors when combined with thermal ablation, but excessive ROS also threatens peritumoral tissue with inflammation. To eradicate tumors and avoid inflammatory sequela, it is necessary to generate ROS in treatment stage and scavenge ROS in prognostic stage. However, it is a great challenge to reverse ROS in different stages. Herein, the "ROS switcher" of MnO₂-coated Prussian blue (PM) is loaded in hyaluronic acid methacrylate (HAMA) hydrogel microspheres, combining ROS generation by Mn-mediated Fenton-like reaction, and ROS scavenging by Fe^3+/2+ electron transfer. Firstly, it is ROS generator that oxidatively damages biomacromolecules in residual tumors, then it is ROS scavenger that reduces pro-inflammatory cytokines and oxidation stress in peritumoral skin_. Glucose oxidase is immobilized in HAMA microspheres to enhance ROS supply by catalyzing glucose into H₂O₂, degrading MnO₂ into Mn²⁺, and providing H₂O₂ for a Fenton-like reaction. After MnO₂ degradation, Prussian blue is gradually exposed and scavenges ROS, thus defending oxidative skin damage and alleviating ROS-stimulated inflammation. In vitro results indicate that the microsphere supplied sustained ROS for up to 5 days, and H₂O₂-degraded PM (0.2 mg mL^-1) scavenged 500 μM H₂O₂. In vivo results confirm that 4/6 breast tumors were eradicated while pro-inflammatory cytokines were significantly reduced with ROS level in peri-tumoral skin. In summary, ROS switcher is developed by Mn-mediated nano-shell peeling and achieves tumor eradication and post-operative skin repair after thermal ablation of the breast tumor.