Biomimetic Coacervate Microdroplets Capable of Generating Nitric Oxide and Photonic Hyperpyrexia for Bacterial Killing and Wound Disinfection

Abstract

Wound bacterial infections pose a serious threat to human health. Nitric oxide (NO) is a broad-spectrum antimicrobial agent and widely participates in immune response, tissue repair, and inflammation regulation. The in situ controllable generation of NO is of crucial importance for the development of NO-based antibacterial agents. Herein, we have constructed a biomimetic, primitive cell-inspired antibacterial coacervate microdroplet for multimode synergistic antibacterial therapy and accelerating wound healing. In this system, the dual-functional photosensitizer indocyanine green (ICG) and the NO prodrug l-arginine (l-Arg) were co-encapsulated into a phospholipid-coated coacervate by liquid–liquid phase separation, yielding a near-infrared (NIR)-activatable NO-releasing platform (IACoac@M). Upon NIR laser irradiation, the loaded ICG not only directly generated the photonic hyperpyrexia for bacterial killing but also performed a photodynamic process for producing singlet oxygen (¹O₂) that further oxidated l-Arg into NO. The NO production suppresses the expression of the bacterial molecular chaperone DnaK, a heat shock protein, promoting the photothermal therapy. By the combination of multiple bactericidal modalities, IACoac@M showed high antibacterial activities against Gram-positive S. aureus and Gram-negative E. coli. Further in vivo animal assays revealed that IACoac@M could effectively eliminate bacteria cells in wound tissue; inhibit inflammatory factors; and promote angiogenesis, collagen deposition, and epidermal regeneration, thereby accelerating the wound healing process. This study provided a rationally designed multifunctional coacervate capable of generating NO and photonic hyperpyrexia for photothermal/photodynamic/gas trimode synergistic antibacterial therapy, offering a potential solution for the treatment of wound bacterial infections.