Cu single-atom embedded g-C3N4 nanosheets rehabilitate multidrug-resistant bacteria infected diabetic wounds via photoswitchable cascade reaction

Abstract To tackle elevated blood glucose, multidrug-resistant (MDR) bacterial infections, and persistent inflammation in diabetic wounds, we present a therapeutic strategy that employs a photoswitch-controlled catalytic cascade reaction, utilizing a photocatalytic material engineered through the synergistic regulation of nitrogen vacancies and single-atom embedding. Under visible light illumination, the N vacancy exist in g-C 3 N 4 (CN) significantly enhances photocatalytic glucose oxidation to regulate the hyperglycemia condition at diabetic wound sites, and the atomically dispersed Cu promotes the generation of •OH and •O 2 – to efficiently eliminate MDR bacteria ( > 99.9%). Under dark conditions, excess ROS are scavenged by Cu/CN, reducing inflammation of wounds and promoting polarization of M2 macrophages. Serum biochemical and vital organs histopathological analyses after 14 days of treatment confirm the biosafety profile of Cu/CN. This photoswitchable cascade reaction effectively treats MDR bacterial-infected diabetic wounds in male mice, highlighting its potential for antibiotic-free therapy with promising clinical translation applications.