Targeted Therapy of Fungal Keratitis Enabled by Iron Nutritional Deprivation Combined With Photothermal Effect

Given the scarcity of targeted antifungal drug and increasing resistance to hormonal drug in pathogens, the therapy of fungal keratitis poses formidable challenges. To fundamentally eliminate resistance, drugs with novel antifungal mechanisms are needed. Upon the crucial demand for iron in the metabolic process of fungal life, inspired by iron nutritional immunity therapy, we proposed selectively targeting fungi to induce iron starvation in pathogens, thus affecting iron transport and energy metabolism, ultimately facilitating fungal killing and corneal repair. A hormone‐free nanodrug system, constructed by hollow polydopamine nanospheres loading with iron chelating agent deferoxamine and modifying with the fungal cell wall analog chitosan oligosaccharide lactate as target molecular, was developed, which not only can target fungal cells and achieve iron nutritional deprivation but also has photothermal treatment capability. Simultaneously, the nanodrug can penetrate the corneal barrier to reach the lesion site and eliminate free radicals and reduce oxidation levels. This work presents a promising antifungal strategy from a nutritional perspective that sheds light on refractory fungal keratitis treatment and its future clinical application.