Antifungal-lnbuilt Metal-Organic-Frameworks Eradicate Candida albicans Biofilms

摘要

Fungal biofilms cause a major clinical problem with a shrinking armamentarium for treatment. Here, the design and synthesis of voriconazole-inbuilt zinc 2-methylimidazolates frameworks (V-ZIF) is reported. Voriconazole is built in through coordination-binding between zinc and voriconazole. These metal-organic-frameworks with inbuilt voriconazole, reduce inadvertent voriconazole-leakage, yield a zero-order release kinetics of voriconazole, aid antifungal penetration in Candida albicans biofilms, and prevent Candida aggregation yielding better dispersal. Once accumulated in an acidic C. albicans biofilm, voriconazole dissociates from the metal-organic framework to cause membrane-damage and killing of inhabiting fungi. Moreover, in a murine model, the V-ZIFs eradicate open-wound infections caused by C. albicans better than voriconazole in solution, with negligible side effects to the healthy tissues of major organs. Thus, V-ZIFs may provide a welcome addition to the antifungal armamentarium currently available for the treatment of fungal biofilms.