Copper-functionalized hydroxyapatite nanoparticles to counteract fungal infections

Drug-resistant fungal pathogens pose an increasing threat to human health. Nanoparticles are promising tools for treating and limiting fungal resistance due to their ability to attack microorganisms via multiple mechanisms. In this work, hydroxyapatite (HA) nanoparticles were synthesized and functionalized with copper by ionic exchange at different solution concentrations (from 0.01 to 0.2 M). The physico-chemical properties of the samples were studied using low-temperature N2 adsorption volumetry, elemental analysis, X-ray diffraction, electron microscopy and IR spectroscopy of adsorbed CO. All the obtained HA particles were poorly crystalline, elongated in the c-axis direction, and had a high specific surface area (ca. 200 m2/g). Copper was incorporated into HA surface layers with a Cu2+ doping content proportional to the initial concentration, reaching a maximum value of 14 %wt. The antifungal activity of the samples was tested against drug-resistant clinical isolates of Cryptococcus neoformans and several Candida species strains (C. parapsilosis, C. krusei, C. tropicalis, C. albicans, C. glabrata, C. auris). Minimal inhibitory concentrations and fungal growth curves were determined. Cytocompatibility evaluation showed that both undoped and Cu-doped HA samples were not toxic to mammalian cells. The Cu-containing HA samples demonstrated potential as effective and safe antifungal agents with wide-spectrum activity, representing a promising candidate for therapeutic approaches against diverse fungal infections.