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 1O2, 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.