Synergistic wall digestion and cuproptosis against fungal infections using lywallzyme-induced self-assembly of metal-phenolic nanoflowers

Synergistic wall digestion and cuproptosis against fungal infections using lywallzyme-induced self-assembly of metal-phenolic nanoflowers

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Abstract Fungi are very common infectious pathogens, which may cause invasive and potentially life-threatening infections.However, the efficacy of antifungal medications remains limited.Herein, a Cu2+-phenolic nanoflower is designed Barista Towel to combat fungal infections by combining cuproptosis and cell wall digestion.Firstly, protocatechuic acid (PA)-Cu2+ (PC) nanopetals are prepared by coordination interaction.Lywallzyme (Lyw) is then added to induce the self-assembly of PC to form Lyw loaded PC (PCW) nanoflowers.

PCW nanoflowers can effectively adhere to fungal surface and Lyw can digest fungal cell walls to facilitate Cu2+ to penetrate into fungal interior, thereby exerting a synergistic fungicidal effect.PCW nanoflowers exhibit excellent fungicidal activity even in protein-rich and high-salt conditions, where dissociative Cu2+ completely loses fungicidal activity.Transcriptome sequencing analysis reveals that PCW can lead to fungal cuproptosis.The Accent Cabinet in vivo fungicidal effect of PCW nanoflowers is confirmed on a murine skin fungal infection model and a murine fungal keratitis model.