Multifunctional Selenium–Sulfur-Doped Carbon Dots Nanozymes with Thioredoxin Reductase Activity for Regenerative Therapy of Infected Wounds

Abstract

Bacterial-infected wounds exhibit delayed healing due to numerous pathological factors, including excessive inflammatory responses, reactive oxygen species (ROS) accumulation, and impaired angiogenesis. Current clinical therapies predominantly employ antimicrobial monotherapy, failing to address the complex interplay among the other pathogenic factors. Herein, we synthesized multifunctional selenium–sulfur-doped carbon dots (SE/S-CDs) nanozymes using selenocystine and cysteine as precursors to simultaneously target multiple pathological hallmarks of infected wounds. Primarily, SE/S-CDs exerted potent antibacterial activity by compromising the integrity of bacterial cell membranes, thereby achieving robust pathogen clearance in infected wounds. Furthermore, owing to the presence of Se–S dynamic bonds, they can specifically activate the thioredoxin reductase (TrxR) pathway, efficiently scavenging ROS and alleviating the inflammatory response. In addition, SE/S-CDs upregulated the hypoxia-inducible factor 1α (HIF-1α) signaling pathway, promoting the expression of proangiogenic genes and accelerating neovascularization and tissue repair. Collectively, SE/S-CDs modulated the infected wound microenvironment through a coordinated “antibacterial–anti-inflammatory–antioxidant–proangiogenic” cascade, demonstrating excellent, integrated therapeutic outcomes. This integrated therapeutic strategy not only exhibits efficacy in infected wound treatment but also holds translational potential for other infection-related and oxidative stress-driven diseases.