NIR photo-responsive injectable chitosan/hyaluronic acid hydrogels with controlled NO release for the treatment of MRSA infections

Due to resistance to common antibiotics, methicillin-resistant Staphylococcus aureus (MRSA) infections pose a significant threat to human health. In this study, we developed an injectable, adhesive, and biocompatible hydrogel with multiple functions. Specifically, carboxymethyl chitosan (CMCS) crosslinked with hyaluronic acid (HA) forms the primary framework of the hydrogel. Subsequently, polydopamine (PDA), 5,10,15,20-tetrakis (4aminophenyl) porphyrin (TAPP), and L-arginine (L-Arg) are incorporated as a photothermal agent, photosensitizer, and nitric oxide (NO) donor, respectively, resulting in the CHDTA hydrogel. Under the combined irradiation of 660 nm and 808 nm near-infrared (NIR) light, the CHDTA hydrogel exhibits both photodynamic therapy (PDT) and photothermal therapy (PTT) effects. Simultaneously, L-Arg reacts with singlet oxygen (1O2), generated via the PDT effect, leading to the production of NO. The CHDTA hydrogel effectively inhibits the activity of Staphylococcus aureus (S. aureus) and MRSA, achieving bactericidal rates of 99.4 % and 98.8 %, respectively, through a combination of PDT, PTT, and NO synergistic antibacterial mechanisms. In vivo studies demonstrate the excellent antibacterial properties and wound healing promotion of the CHDTA hydrogel in MRSA-infected animal wound models. The hydrogel system developed in this study integrates multiple functional design concepts and serves as a potential therapeutic platform for combating MRSA infections.