Self-supply of H2O2 and O2 by a composite nanogenerator for chemodynamic therapy/hypoxia improvement and rapid therapy of biofilm-infected wounds

Bacterial wound infection is a major challenge to human health worldwide. In this study, a composite nano -generator, CaO2@ZIF-67-PLL, was fabricated via a bottom-up approach with chemodynamic therapy (CDT)/ hypoxia improvement for rapid therapy of biofilm-infected wounds. Under a pathologically acidic microenvi-ronment, the out layer ZIF-67 can be decomposed to rapidly release Co2+ and CaO2; Subsequently, the unpro-tected CaO2 reacts with H2O to produce O2 and H2O2. The self-supply of O2 relieves hypoxia and inflammatory response induced by infections, while the generated H2O2 and poly -L-lysine (PLL) exhibited synergistic strong anti-biofilm capability against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) as assessed by reactive oxygen species (ROS) generation, membrane permeability change, ATP reduction, o-nitrophenyl-beta-d-galactopyranoside (ONPG) hydrolysis and intracellular component leakage. Meanwhile, CaO2@ZIF-67-PLL exhibited good cytocompatibility and promoted the adhesion, proliferation, and migration of NIH-3T3 cells by enhancing the expression of wound healing-related genes (TGF-beta 1, VEGF, alpha-SMA, Col I, Col III, and Wnt-5a). Notably, CaO2@ZIF-67-PLL could significantly improve the healing process of S. aureus-infected wounds via suppressed inflammatory responses, enhanced collagen disposition and angiogenesis, and stimulated HIF-1 alpha, CD31, and Wnt-5a/beta-Catenin signaling pathways. These results indicated the potential of CaO2@ZIF-67-PLL nanogenerator for clinical application in infected wound treatment.