Regulatable nanomotors for NIR-responsive, NO release and cuproptosis: Synergistic antifungal therapy

Antibiotics are crucial for the treatment of fungal infections. Yet the issue of antimicrobial resistance is becoming increasingly severe due to inappropriate use. Consequently, the development of novel antimicrobial technologies is imperative. The nanomotor designed in this study was capable for penetrating the infected areas, and effectively combating fungi. The nanomotor consists of polydopamine chelated with copper ions and loaded with N,N'-Di-sec-butyl-N,N'-dinitroso-1,4-phenylenediamine (BNN6), and coated with hyaluronic acid, with asymmetric gold modification (CPBHA). Under 808 nm irradiation, the thermophoretic effect directed the movement of the nanomotor. At high temperatures, BNN6 released NO, which could modulate the speed of CPBHA. NO can not only promote angiogenesis and regulate macrophage polarization, but also accelerate the wound repair process. Moreover, Cu²⁺ could induce lipid peroxidation and cuproptosis, leading to fungal cell death. In addition, CPBHA significantly accelerates wound healing in a mouse model infected with C. albicans, achieving a healing rate of approximately 97 % by the ninth day, fully demonstrating its potential as a therapeutic agent.