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The development of effective antifungal agents remains a big challenge in view of the close evolutionary relationship between mammalian cells and fungi. Moreover, rapid mutations of fungal receptors at the molecular level result in the emergence of drug resistance. Here, with low tendency to develop drug-resistance, the subcellular organelle mitochondrion is exploited as an alternative target for efficient fungal killing by photodynamic therapy (PDT) of mitochondrial-targeting luminogens with aggregation-induced emission characteristics (AIEgens). With cationic isoquinolinium (IQ) moiety and proper hydrophobicity, three AIEgens, namely, IQ-TPE-2O, IQ-Cm, and IQ-TPA, can preferentially accumulate at the mitochondria of fungi over the mammalian cells. Upon white light irradiation, these AIEgens efficiently generate reactive 1 O 2 , which causes irreversible damage to fungal mitochondria and further triggers the fungal death. Among them, IQ-TPA shows the highest PDT efficiency against fungi and negligible toxicity to mammalian cells, achieving the selective and highly efficient killing of fungi. Furthermore, we tested the clinical utility of this PDT strategy by treating fungal keratitis on a fungus-infected rabbit model. It was demonstrated that IQ-TPA presents obviously better therapeutic effects as compared with the clinically used rose bengal, suggesting the success of this PDT strategy and its great potential for clinical treatment of fungal infections.

Mitochondria-Specific Aggregation-Induced Emission Luminogens for Selective Photodynamic Killing of Fungi and Efficacious Treatment of Keratitis