A Membrane‐Targeted Photosensitizer Prevents Drug Resistance and Induces Immune Response in Treating Candidiasis

Abstract Candida albicans ( C. albicans ), a ubiquitous polymorphic fungus in humans, causes different types of candidiasis, including oral candidiasis (OC) and vulvovaginal candidiasis (VVC), which are physically and mentally concerning and financially costly. Thus, developing alternative antifungals that prevent drug resistance and induce immunity to eliminate Candida biofilms is crucial. Herein, a novel membrane‐targeted aggregation‐induced emission (AIE) photosensitizer (PS), TBTCP‐QY, is developed for highly efficient photodynamic therapy (PDT) of candidiasis. TBTCP‐QY has a high molar absorption coefficient and an excellent ability to generate 1 O 2 and •OH, entering the interior of biofilms due to its high permeability. Furthermore, TBTCP‐QY can efficiently inhibit biofilm formation by suppressing the expression of genes related to the adhesion ( ALS3 , EAP1 , and HWP1 ), invasion ( SAP1 and SAP2 ), and drug resistance ( MDR1 ) of C. albicans , which is also advantageous for eliminating potential fungal resistance to treat clinical infectious diseases. TBTCP‐QY‐mediated PDT efficiently targets OC and VVC in vivo in a mouse model, induces immune response, relieves inflammation, and accelerates the healing of mucosal defects to combat infections caused by clinically isolated fluconazole‐resistant strains. Moreover, TBTCP‐QY demonstrates excellent biocompatibility, suggesting its potential applications in the clinical treatment of OC and VVC.