Photosensitizer‐Amplified Antimicrobial Materials for Broad‐Spectrum Ablation of Resistant Pathogens in Ocular Infections

Author:

Lochenie Charles12,Duncan Sheelagh1,Zhou Yanzi12,Fingerhut Leonie1,Kiang Alex1,Benson Sam12,Jiang Guanyu3,Liu Xiaogang3,Mills Bethany1,Vendrell Marc12ORCID

Affiliation:

1. Centre for Inflammation Research University of Edinburgh 4‐5 Little France Drive Edinburgh EH16 4UU UK

2. IRR Chemistry Hub Institute for Regeneration and Repair 4‐5 Little France Drive Edinburgh EH16 4UU UK

3. Fluorescence Research Group Singapore University of Technology and Design 8 Somapah Road Singapore 487372 Singapore

Abstract

AbstractThe 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, a new class of benzodiazole‐paired materials is designed as highly potent PDT agents with broad‐spectrum antimicrobial activity upon illumination with nontoxic light. The results mechanistically demonstrate that the energy transfer and electron transfer between nonphotosensitive and photosensitive benzodiazole moieties embedded within pathogen‐binding peptide sequences result in increased singlet oxygen generation and enhanced phototoxicity. Chemical optimization renders PEP3 as a novel PDT agent with remarkable activity against MDR bacteria and fungi as well as pathogens at different stages of development (e.g., biofilms, spores, and fungal hyphae), which also prove 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.

Funder

Horizon 2020

European Research Council

Engineering and Physical Sciences Research Council

UK Research and Innovation

Publisher

Wiley

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