Self-assembled copper-phenolic nanoparticles for antimicrobial therapy by triggering Fenton reaction and cuproptosis-like bacterial death

Abstract

The increasing prevalence of antibiotic-resistant bacteria poses a significant threat to global health. This study introduces poly(ethylene glycol)-copper-tannic acid nanoparticles (PCT NPs) as a novel therapeutic strategy for treating bacterial infections. PCT NPs, synthesized via self-assembly of Cu²⁺, tannic acid, and poly(ethylene glycol), exhibit pH-responsive release of Cu²⁺, which generates reactive oxygen species (ROS) and depletes glutathione (GSH) in bacterial cells, leading to cuproptosis-like bacterial death. PCT NPs also demonstrate strong adhesion to bacterial surfaces, enhancing their ability to deliver Cu²⁺ directly to bacterial cells. In vitro experiments demonstrate strong bactericidal activity against MRSA and P. aeruginosa. In vivo studies in murine models of skin and lung infections confirm the efficacy of PCT NPs in reducing bacterial load and promoting wound healing. This work highlights PCT NPs as a promising non-antibiotic alternative for combating deep-seated bacterial infections.