Bismuth Sulfide Microneedle Patch for MRSA Biofilm Removal via Oxidative Stress Amplification

Abstract Traditional photodynamic biofilm removal is hindered by biofilm barriers, hypoxia, and bacterial antioxidant defenses. Herein, a soluble microneedle (MN) patch functionalized with Ga 3 ⁺‐catechol‐coated bismuth sulfide (BSPG) as a light/pH‐activatable nanosynergist is developed to amplify oxidative stress for effective biofilm elimination. Urchin‐like BSPG can penetrate bacteria and release Ga 3 ⁺ to disrupt the bacterial antioxidant system by inhibiting the activity of superoxide dismutase and catalase in acidic biofilm environments. Under laser irradiation, BSPG generates superoxide anions and hydrogen peroxide via type I photodynamic behavior, which synergize with Ga 3 ⁺ to significantly enhance antibacterial/antibiofilm activity. RNA transcriptomic analysis reveals that BSPG + laser treatment disrupts bacterial metabolism, reduces ATP production, and increases bacterial permeability. Furthermore, BSPG + laser treatment disrupts bacterial antioxidant repair mechanisms, leading to a sharp increase in oxidative stress and lipid peroxide accumulation, significantly damaging bacterial survival. Additionally, in vivo experiments demonstrate that BSPG MN patch breaks through biological barriers for efficient delivery of BSPG, thereby BSPG MN patch can remove bacterial biofilms, reduce inflammation, and accelerate wound healing. These results suggest BSPG as a promising treatment for bacterial biofilm‐infected wounds.