Nitric Oxide-Enhanced Chitosan-Based Nanoparticles for Dual-Mode Photothermal and Photodynamic Therapy in Infected Wounds

Bacterial infections pose a significant challenge to global health, as conventional treatments frequently cause side effects and resistance. Phototherapy, encompassing photothermal therapy (PTT) and photodynamic therapy (PDT), emerges as a viable alternative, eradicating bacteria through heat and reactive oxygen species (ROS). However, excessive heat and ROS can exacerbate local inflammation and comlicate healing. To address these challenges, we developed a novel chitosan-based nanoparticle (NPs) encapsulating S-nitrosoglutathione (GSNO) and indocyanine green (ICG), termed as GSNO/ICG@NPs. This biocompatible nanosystem integrates the triple synergistic effects of nitric oxide (NO) release, PTT, and PDT. The stable and uniformly shaped GSNO/ICG@NPs were synthesized via a charge-driven self-assembly method with efficient loading of GSNO and ICG. Upon irradiation with an 808 nm near-infrared (NIR) laser, GSNO/ICG@NPs rapidly generate heat and 1 O 2 , effectively eliminating bacteria. Simultaneously, the photothermal effect releases NO from GSNO, modulates inflammation, promotes neovascularization, and supports tissue repair. In vitro and in vivo studies demonstrated that GSNO/ICG@NPs significantly enhance antibacterial activity, reduce inflammation, and promote angiogenesis. It effectively eradicated biofilms and accelerated wound healing in a Staphylococcus aureus -infected mouse skin model. These findings highlight GSNO/ICG@NPs as a promising alternative to antibiotics for treating infected wounds via synergistic therapy involving balanced NO release, PTT, and PDT.