Reactive oxygen species switcher via MnO2-coated Prussian blue loaded hyaluronic acid methacrylate hydrogel microspheres for local anti-tumor treatment
Huijie Han, Shiqi Wang, Mohammad‐Ali Shahbazi, Inge S. Zuhorn, Zhengwei Cai, Jie Chen, Jiachen Li, Yu Chen, Yawei Du, Raquel Bártolo, Liang Chen, Hélder A. Santos, Wenguo Cui
Abstract
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 MnO 2 -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 H 2 O 2 , degrading MnO 2 into Mn 2+ , and providing H 2 O 2 for a Fenton-like reaction. After MnO 2 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 H 2 O 2 -degraded PM (0.2 mg mL −1 ) scavenged 500 μM H 2 O 2 . 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.