A mitochondria-targeted aggregation-induced emission photosensitizer for eradication Candida biofilms and treating oral ulcer

Abstract

With increasing drug resistance, Candida infections have posed serious threats to public health. Photodynamic therapy harnesses light to destroy pathomycete, providing a smart strategy for combating of Candida infections. However, due to lack of organelle targeting ability and bad extracellular polymeric substances penetrability, current photosensitizers (PSs) are far from desirable to clean biofilms and fight against drug resistance. Herein, a mitochondrion targeting aggregation-induced emission PS, LIQ-TPA-TZ, was developed for the efficient photodynamic treatment of oral Candida infection. LIQ-TPA-TZ has good singlet oxygen and hydroxyl radical generation ability, which can efficiently kill the Candida guilliermondii (C. guilliermondii) and eradicate the biofilm. It not only causes mitochondrial damage by disruption of mitochondrial respiratory chain and oxidative stress-related gene but also inhibits fungal adhesion and filamentous growth to prevent Candida colonization, mycelia growth and biofilm formation, which is favorable for eliminating the potential drug resistance. In the mouse oropharyngeal Candida biofilm infection model, LIQ-TPA-TZ significantly eliminates infection, alleviates inflammation, and accelerates mucosal defect healing. This study provides a favorable strategy for confronting drug resistance, which may be a potential Candidate for the treatment of Candida infection.

Keywords

aggregation-induced emission / biofilm / candida infection / mitochondrial targeting photosensitizer / photodynamics therapy

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2025 The Author(s). Smart Molecules published by John Wiley & Sons Australia, Ltd on behalf of Dalian University of Technology.