Advanced Palladium Nanosheet‐Enhanced Phototherapy for Treating Wound Infection Caused by Multidrug‐Resistant Bacteria

Abstract With the increasing spread of multidrug‐resistant (MDR) bacteria worldwide, it is needed to develop antibiotics‐alternative strategies for the treatment of bacterial infections. This work develops a multifunctional single‐component palladium nanosheet (PdNS) with broad‐spectrum and highly effective bactericidal activity against MDR bacteria. PdNS exerts its endogenous nanoknife (mechanical cutting) effect and peroxidase‐like activity independent of light. Under near‐infrared region (NIR) light irradiation, PdNS exhibits photothermal effect to produce local heat and meanwhile possesses photodynamic effect to generate 1 O 2 ; notably, PdNS has catalase‐like activity‐dependent extra photodynamic effect upon H 2 O 2 addition. PdNS+H 2 O 2 +NIR employs a collectively synergistic mechanism of nanoknife effect, peroxidase/catalase‐like catalytic activity, photothermal effect, and photodynamic effect for bacterial killing. PdNS+H 2 O 2 +NIR causes compensatory elevated phospholipid biosynthesis, disordered energy metabolism, increased cellular ROS levels and excessive oxidative stress, and inhibited nucleic acid synthesis in bacteria. In mice, PdNS+H 2 O 2 +NIR gives >92.7% bactericidal rates at infected wounds and almost the full recovery of infected wounds, and it leads to extensive down‐regulation of proinflammatory pathways and comprehensive up‐regulation of wound healing pathways, conferring elevated inflammation resolution and meanwhile accelerated wound repair. PdNS+H 2 O 2 +NIR represents a highly efficient nanoplatform for photoenhanced treatment of superficial infections.