Hydrogel microreactor integrated double cascade reactions for synergistic bacterial inactivation and wound disinfection

Catalytic bacterial inactivation mediated by peroxidase nanomimics, which converts hydrogen peroxide (H2O2) to hydroxyl radical (•OH) with high toxicity, has been emerged as a promising solution to combat bacterial infections and antibiotic resistance. However, the bacterial inactivation efficacy was often restricted by the low catalytic activity of peroxidase nanomimics and the short half-life and limited diffusion distance of •OH. Here, we developed a hydrogel microreactor (GHAP) integrated double cascade reactions to sequentially generate •OH and nitric oxide (NO) for synergistic bacterial inactivation, where NO offers a complementary effect to compensate •OH for incomplete bacterial inactivation. The GHAP was fabricated by the coencapsulation of glucose oxidase (GOx), hemoglobin (Hb) and zeolitic imidazolate framework-8 loaded with arginine (Arg) in polyacrylamide (pAAm) hydrogel microsphere. The presence of glucose can trigger GHAP to sequentially generate •OH and NO though the successive coupling of GOx with Hb and Arg. The pAAm microsphere was demonstrated to enhance cascade catalytic efficiencies and shield GHAP against harsh conditions due to its confinement effect. Importantly, compared with single •OH/NO-generated cascade systems, the superiority of GHAP was highlighted by the synergistic antibacterial effects of •OH and NO, which thereby endows GHAP with a greatly enhanced antibacterial performance and an exceptional broad-spectrum antibacterial ability. In vivo experiments in a mouse model demonstrated that GHAP could be used for wound disinfection with minimal side effects. This work opens a new avenue for the rational design of biomimetic reactors for biomedical applications.