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 1O2; notably, PdNS has catalase-like activity-dependent extra photodynamic effect upon H2O2 addition. PdNS+H2O2+NIR employs a collectively synergistic mechanism of nanoknife effect, peroxidase/catalase-like catalytic activity, photothermal effect, and photodynamic effect for bacterial killing. PdNS+H2O2+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+H2O2+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+H2O2+NIR represents a highly efficient nanoplatform for photoenhanced treatment of superficial infections.