NIR-activated Quercetin-based Nanogels Embedded with CuS Nanoclusters for the Treatment of Drug-resistant Biofilms and Accelerated Chronic Wound Healing

We have developed multifunctional nanogels with antimicrobial, antioxidant, and anti-inflammatory properties, facilitating rapid wound healing. To prepare the multifunctional nanogels, we utilized quercetin (Qu) and a mild carbonization process to form carbonized nanogels (CNGs). These CNGs possess excellent antioxidative and bacterial targeting properties. Subsequently, we utilized the Qu-CNGs as templates to prepare nanogels incorporating copper sulfide (CuS) nanoclusters, further enhancing their functionality. Notably, the CuS/Qu-CNGs nanocomposites demonstrated an exceptional minimum inhibitory concentration against tested bacteria, approximately 125-fold lower than monomeric Qu or Qu-CNGs. This enhanced antimicrobial effect was achieved by leveraging near-infrared II (NIR-II) light irradiation. Additionally, the CuS/Qu-CNGs exhibited efficient penetration into the extracellular biofilm matrix, eradicating methicillin-resistant -associated biofilms in diabetic mice wounds. Furthermore, the nanocomposites were found to suppress proinflammatory cytokines, such as IL-1β, at the wound sites while regulating the expression of anti-inflammatory factors, including IL-10 and TGF-β1, throughout the recovery process. The presence of CuS/Qu-CNGs promoted angiogenesis, epithelialization, and collagen synthesis, thereby accelerating wound healing. Our developed CuS/Qu-CNGs nanocomposites have great potential in addressing the challenges associated with delayed wound healing caused by microbial pathogenesis.