Copper‐Polyphenol Nanocomplexes with Peroxidase‐Like Activity for Enhanced Fungal Eradication

Abstract The increasing severity of fungal infections globally and the limited availability of effective treatments necessitate novel therapeutic strategies. In this study, we prepared copper‐polyphenol nanocomplexes (CPE NPs) through a one‐step synthetic process by the coordination self‐assembly of copper sulfate (CuSO 4 ), protocatechuic acid (PA), and ϵ‐poly‐L‐lysine (EPL). CPE NPs demonstrated peroxidase‐like activities, which could catalyze H 2 O 2 to generate hydroxyl radicals (⋅OH) to effectively eradicate fungi. CPE NPs were stable in a physiological neutral environment. However, since metal‐phenolic coordination interaction was unstable in acidic pH, CPE NPs could be dissociated in acidic environments, such as fungal infection sites, leading to effective release of Cu 2+ and EPL, thereby exerting antifungal effects. CPE NPs exhibited excellent fungicidal ability at both pH 7.4 and 6.0 against Candida albicans and Aspergillus flavus . More importantly, CPE NPs could effectively eradicate fungi in 20 % Sabouraud dextrose broth (SDB) medium containing rich inorganic salts and proteins, in which dissociative Cu 2+ completely lost its fungicidal ability. In summary, CPE NPs could effectively deliver Cu 2+ to fungal surface for enhanced fungal eradication by generating ⋅OH, highlighting their great potential as a promising nano‐therapeutic agent for the treatment of fungal infections.