Cu-Single Atoms/Clusters-Nanoenzymes Trigger and Integrate Tandem Effect to Synchronously Boost Antifungal and Anti-Inflammation for Fungal Keratitis.

Abstract

Fungal keratitis (FK) is an extremely blinding infectious ocular surface disease. Clinically, there are three major challenges in the topic drug treatment of FK: poor corneal permeability, poor antifungal effect, and inability to simultaneously reduce the inflammation accompanying the infection. In this work, atomically dispersed Cu-N₄ and Cu nanoclusters is designed loaded on the a small-sized positively charged CDs (denoted as Cu-SA/NC@CDs) is designed to fabricate Cu-Needs. The Cu-Needs exhibited excellent corneal permeability, which could can temporarily open the tight connections between corneal cells. More importantly, Cu-Needs achieve rapid fungal elimination and eradication through energy depletion in fungus in the early stage of FK. Subsequently, Cu-Needs effectively eliminated ROS and alleviated the inflammation in cornea tissue. This work proposes a strategy for the whole-process intervention of fungal keratitis by regulating the microenvironment of single-atom centers and nanoclusters through a tandem effect and enhancing catalytic activity. Conclusively, the excellent biosafety (biocompatibility, irritancy, ocular local toxicity and systemic toxicity) made Cu-Needs a great potential strategy in clinical treatment of FK and other serious infectious diseases.