Quaternary Ammonium-Functionalized Membrane-Anchored Photosensitizer against Multidrug-Resistant Bacterial Infections.

Abstract

The discovery of new antimicrobial medications has not kept up with the evolution of bacterial resistance, and infections with drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), continue to pose a serious threat to global public health. Antimicrobial photodynamic therapy (aPDT), as an alternative strategy, produces reactive oxygen species (ROS) under light activation and kills drug-resistant bacteria through oxidative damage. Nevertheless, conventional photosensitizers (PSs) are limited by aggregation-caused quenching, inadequate bacterial selectivity, and off-target cytotoxicity. Quaternary ammonium salts (QASs) can preferentially accumulate on bacterial membranes through electrostatic interactions and disrupt the bacterial membranes. The quaternary ammonium PS PK4, reported here has a triphenylamine unit that enhances ROS production. Under white light irradiation, PK4 produces abundant ROS that oxidatively damage bacterial membranes, while exhibiting high photostability and minimal dark toxicity. In an MRSA-infected wound model, PK4-mediated phototherapy can reduce inflammation, accelerate wound healing, and enhance collagen deposition without systemic toxicity, providing a promising aPDT strategy for combating drug-resistant bacterial infections.