Cell membrane-derived nanotherapeutic for combating Candida albicans infections

Candida albicans ( C. albicans ) is a major fungal pathogen responsible for infections ranging from superficial mucosal disease to life-threatening systemic candidiasis. Effective treatment remains difficult due to the pathogen's adaptability, biofilm-associated resistance, limited antifungal drug classes, and rising drug resistance. Here, we developed cellular nanodiscs made with macrophage membrane (denoted "MФ-NDs") as a therapeutic strategy against C. albicans infections. MФ-NDs preserved native macrophage membrane protein receptors and exhibited excellent stability, enabling them to mimic macrophage-fungus interactions. Mechanistically, MФ-NDs exert antifungal activity through two complementary pathways: directly disrupting the fungal membrane to induce intracellular content leakage and indirectly enhancing host immunity by boosting macrophage antifungal function. In vitro , MФ-NDs inhibited fungal growth and biofilm formation in a dose-dependent manner. In a murine model of systemic candidiasis, MФ-ND treatment reduced fungal burden in major organs and improved survival. These findings highlight MФ-NDs as a dual-action nanotherapeutic with potential for combating invasive C. albicans infections.