Coordination-driven self-assembled nanozyme-loaded GelMA microneedles for enhanced photodynamic therapy of diabetic infected wounds

Abstract

Infected diabetic wounds, particularly those complicated by multidrug-resistant bacteria, pose a significant clinical challenge due to the limited efficacy of conventional debridement and antibiotic therapies. Photodynamic therapy (PDT) has emerged as a promising antimicrobial strategy. However, its therapeutic potential is severely hampered by the hypoxic microenvironment of diabetic wounds. This study aimed to develop a multifunctional nanozyme integrated microneedle system, termed GM@MnFC, within a therapeutic framework that combines material design, delivery strategy, and microenvironment modulation. MnFC nanoparticles were constructed through coordination driven self assembly of Fmoc-L-leucine, Mn²⁺, and the photosensitizer chlorin e6 (Ce6). The incorporated Mn²⁺ endowed the nanoparticles with intrinsic catalase-like activity. This enabled in situ oxygen generation from pathological hydrogen peroxide accumulated in diabetic wounds, thereby overcoming the oxygen dependency of PDT. Loading MnFC into dissolving gelatin methacryloyl (GelMA) microneedles achieved efficient deep tissue delivery to target bacteria residing in dermal layers. In vitro studies demonstrated that MnFC possessed excellent catalase-like activity and efficient singlet oxygen generation under 660-nm laser irradiation, exhibiting potent antibacterial efficacy against both Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA). GM@MnFC microneedle treatment significantly accelerated wound closure, enhanced re-epithelialization and collagen deposition, and favorably regulated inflammatory cytokine expression in a diabetic rat model of MRSA-infected wounds. Biosafety evaluations confirmed the excellent biocompatibility of this system. This study presents an innovative strategy exploiting pathological by-products of diabetic wounds to fuel antimicrobial therapy, thereby providing valuable insights for designing multifunctional nanomedicine platforms for chronic wound management.