Self-assembled protein nanosheets with synergistic enzyme cascade and phototherapy for bacterial infection wound...

Bacterial Infection wound healing remains a significant clinical challenge due to persistent drug-resistant bacterial infections and inadequate therapeutic strategies. To overcome these limitations, we engineered a multifunctional two-dimensional (2D) protein nanosystem that synergistically combines enzymatic catalysis, photodynamic therapy (PDT), and photothermal therapy (PTT) for enhanced antimicrobial efficacy and pro-regenerative activity. Utilizing an interfacial self-assembly approach, we co-localized glucose oxidase (GOX) and horseradish peroxidase (HRP) with the photosensitizer protoporphyrin IX (PpIX) and photothermal agent indocyanine green (ICG) into ultrathin nanosheets. This integrated system operates through three complementary mechanisms: (1) GOX-HRP enzymatic cascade generating bactericidal hydroxyl radicals (·OH) from endogenous glucose, (2) PpIX-mediated ROS production under near-infrared (NIR) irradiation, and (3) ICG-induced localized hyperthermia. These combined effects overcome the limitations of individual therapies. Comprehensive in vitro and in vivo evaluations demonstrated remarkable broad-spectrum antimicrobial activity coupled with significant wound healing promotion. This multifunctional nanoplatform represents a promising therapeutic strategy for resistant wound infections while simultaneously addressing tissue regeneration needs.