The Polymer Society of Korea

Abstract

Fungal infections pose a serious threat to global human health fueled by the increase in immunosuppressive therapies. The emergence of multidrug resistance with limited options of current antifungal drugs are a further constraint. There is thus a clear and unmet need to identify therapeutic targets and develop alternative classes of antifungal agents. Here, we hypothesize that dual targeting of key regulatory genes of fungal cell wall synthesis can synergistically inhibit fungal growth. Based on iterative designs, we generate a small library of fungal-targeted nanoconstructs, and identify a lead construct that shows preferential accumulation in fungal cells over mammalian cells and leads to prominent antifungal effects in vitro. We further show that FTNx is highly effective in a mouse model of disseminated candidiasis, demonstrating diminished fungal growth and enhanced survival rate. This strategy appears promising as an effective treatment for fungal infections in mammalian hosts