H2S Donor Functionalized Molecular Machine for Combating Multidrug-Resistant Bacteria Infected Chronic Wounds

Abstract

Chronic wounds are worldwide medical challenge due to the complex and multifaceted etiologies, including bacterial infection, persistent inflammation, and impaired angiogenesis. Developing a comprehensive strategy integrating antibiosis and anti-inflammation to promote revascularization and accelerate wound healing is highly desirable. Nevertheless, current therapeutic methods still face two major challenges: (1) how to combat bacterial drug resistance. (2) how to achieve spatiotemporal control over bacterial elimination and inflammation reduction. To address these issues, a novel H2S donor functionalized molecular machine (MM), ACR-DM-HS, was developed. It selectively binds to and disturbs the bacterial membrane through a light-active vibronic-driven mechanochemical action (VDA), which synergizes with photodynamic therapy (PDT) to efficiently eradicate multidrug-resistant bacteria and biofilms, and conquers the evolution of bacterial resistance. Furthermore, it releases H2S in infected tissues to scavenge excess reactive oxygen species (ROS), inhibit the secretion of inflammatory factors, promote angiogenesis and accelerate the healing of diabetic wounds in vivo. This work provides an integrated strategy combining antibiotic and anti-inflammation to treat with multidrug resistance bacterial infected chronic wounds.