A GSH-scavenging and synthesis-blocking microneedle patch for augmenting photodynamic eradication of diabetic wound biofilm

Abstract

Infected diabetic wound represents a significant clinical challenge, largely due to persistent bacterial biofilm infection that impede healing process. Photodynamic therapy (PDT), an emerging antibiofilm strategy, uses photosensitizers to yield reactive oxygen species (ROS) upon illumination, which oxidatively destroy bacteria and thus combat biofilm‑associated infections. Nevertheless, the efficacy of PDT is substantially undermined by restricted ROS diffusion through compact biofilm structures and, the rapid ROS neutralization by overexpressed reduced glutathione (GSH) within biofilm microenvironment. Current GSH-depletion strategies predominantly focus on eliminating pre-existing GSH, leaving the critical issue of its continuous synthesis unaddressed. To overcome this limitation, we developed a GSH-scavenging and synthesis-blocking microneedle patch (MN/CuTCPP@BSO) for enhanced photodynamic eradication of diabetic wound biofilm. The patch incorporates GSH synthesis inhibitor L-buthionine sulfoximine (BSO) onto copper-tetrakis (4-carboxyphenyl) porphyrin (CuTCPP) nanosheets. We demonstrate that CuTCPP effectively eliminates overexpressed GSH in biofilm, while BSO concurrently blocks its production. This dual-pathway suppression of bacterial antioxidant system synergistically minimizes ROS clearance. Furthermore, the microneedle platform ensures deep penetration of therapeutic agents into biofilm. In vitro and in vivo evaluations collectively verify that MN/CuTCPP@BSO potently enhances ROS generation, effectively eradicates biofilm, and promotes wound healing through Cu2+-mediated angiogenesis, offering a robust and safe strategy for treating biofilm infections in diabetic wound.