Photosensitizer-Amplified Antimicrobial Materials for Broad-spectrum Ablation of Resistant Pathogens in Ocular Infections.

The emergence of multidrug resistant (MDR) pathogens and the scarcity of new potent antibiotics and antifungals are one of the biggest threats to human health. Antimicrobial photodynamic therapy (aPDT) combines light and photosensitizers to kill drug-resistant pathogens; however, there are limited materials that can effectively ablate different classes of infective pathogens. In the present work, we have designed a new class of benzodiazole-paired materials as highly potent PDT agents with broad-spectrum antimicrobial activity upon illumination with non-toxic light. Our results mechanistically demonstrate that the energy transfer and electron transfer between non-photosensitive and photosensitive benzodiazole moieties embedded within pathogen-binding peptide sequences result in increased singlet oxygen generation and enhanced phototoxicity. Chemical optimization rendered PEP3 as a novel PDT agent with remarkable activity against MDR bacteria as well as pathogens at different stages of development (e.g., biofilms, spores, and fungal hyphae), which also proved effective in an ex vivo porcine model of microbial keratitis. The chemical modularity of this strategy and its general compatibility with peptide-based targeting agents will accelerate the design of highly photosensitive materials for antimicrobial PDT. This article is protected by copyright. All rights reserved.