Unearth the ultrapotent intrinsic fungicidal efficacy of the surface-piercing CuFeSe2-PVP nano-blade

The critical shortage of antifungal drugs and increasingly emerged resistant fungi urgently call for the development of novel fungicidal agents with translational potential. Although nanodrugs compose a new antifungal arsenal, the fungicidal efficacy barely exceeds clinical molecules. In this study, a CuFeSe2-PVP nano-blade, is unexpectedly discovered with ultrapotent intrinsic fungicidal efficacy. This nanostructure is facilely fabricated by a specific aqueous precipitation method with the nucleation of tetragonal eskebornite CuFeSe2 at PVP chains. The unique semiconductor CuFeSe2-PVP demonstrates superior antifungal activity than the commonly used small-molecule drugs and metal nanoparticles in both planktonic fungi and biofilm. Intriguingly, electron microscopy visualizes that the nano-blades cut fungal membranes with fungi surfaces inserted by the blades. Such a membrane-piercing effect results in the loss of important intracellular components, including nucleic acids, proteins, and potassium ions. Increased intracellular reactive oxygen species (ROS) is also observed. Encouragingly, in mice with subcutaneous fungal infection, the nanodrug achieves absolute fungi clearance, effectively alleviating inflammation and promoting collagen fiber recovery. Moreover, the excellent biocompatibility of CuFeSe2-PVP promises great potential for further translation. This study not only provides a novel fungicidal drug candidate, but also inspires the future design of anti-fungal nanomedicine.