Engineered Nile Red Derivatives-Mediated Efficient Phototherapy Against Drug-Resistant Bacteria and Monkeypox Virus

Abstract

The escalating threats of antimicrobial resistance and monkeypox virus infections pose a significant challenge to public health, necessitating innovative therapeutic approaches. Developing materials with balanced photodynamic and photothermal effects for the elimination of broad-spectrum drug-resistant bacteria and inactivation of the monkeypox virus remains a formidable task. Herein, we prepared a series of Nile Red derivatives by a donor rotation and charge transfer enhancement strategy, identifying 5-(dicyanomethylene)-9-[4-(bis(4-methoxyphenyl)amino)phenyl]-7a,12a-dihydro-5H-benzo[a]phenoxazine (TPAOMCN)-featuring alkoxy-triphenylamine and malononitrile, as the optimal candidate. TPAOMCN demonstrated extended near-infrared absorption, enhanced intersystem crossing (ISC) efficiency, and intense molecular motions, enabling dual-modal phototherapy. Electrospun TPAOMCN nanofibers (NFs) with submicron-scale diameter achieved >50°C temperature elevation and excellent reactive oxygen species (ROS) generation under irradiation. In methicillin-resistant S. aureus (MRSA)-induced wound infection and vaccinia virus-mediated tail-scarred models, TPAOMCN NFs effectively eliminated MRSA colonies and reduced viral load through physical disruption of pathogen membranes, thermal denaturation of viral capsids, and ROS-mediated oxidation of biomolecules, while suppressing inflammation and accelerating angiogenesis-mediated tissue repair. This study not only established a molecular engineering strategy for Nile Red to achieve prime PDT-PTT performance but also provided a paradigm for advancing dual-functional phototherapeutic platforms against emerging antimicrobial threats and monkeypox virus infections.

Keywords

drug-resistant bacteria / monkeypox virus / Nile Red derivatives / photodynamic therapy / photothermal therapy

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