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 Staphylococcus aureus-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.