Metformin-Loaded J-AuPPS for Infected Diabetic Wound Treatment

Fuli Yin¹Lingkai Yang¹Haojie Shan¹Yuan Ge Li¹Yongfeng Zhou²Xiaowei Yu^1*

• ¹Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
• ²School of Chemistry and Chemical Engineering Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, Shanghai, China

Introduction: Infected diabetic wounds pose a significant clinical challenge owing to the complex wound microenvironment. Various multifunctional synergistic therapeutic nanomaterials have been successfully developed to treat diabetic infected wounds. Objective: A Janus Au–porphyrin polymersome heterostructure loaded with metformin (Met@J-AuPPS) is constructed and presented. Methods: Porphyrin polymersome vesicles loaded with metformin (Met@PPS) was synthesized by supramolecular polymerization enhanced self-assembly. Metformin-loaded Janus gold-porphyrin polymersome (Met@J-AuPPS) was synthesized by photocatalytic synthesis method. Transmission electron microscope (TEM), scanning electron microscope (SEM), UV-vis absorption spectrum and ELISA experiment were used to detect the morphology, structure, photothermal properties and drug release properties of Met@J-AuPPS. The effects of Met@J-AuPPS on the proliferation and activity of HUVECs were detected by CCK-8 test, scratch test, Transwell test and tube formation test. The antibacterial and antibiofilm abilities of Met@J-AuPPS were detected by blood plate test, crystal violet staining, SEM of biofilm and bacterial live/dead staining. Imaging and histological staining were used to detect the efficacy of Met@J-AuPPS in treating diabetic wound infections in vivo. Results: Excellent photothermal antibacterial performance against gram-positive methicillin-resistant Staphylococcus aureus (MRSA), gram-negative extended-spectrum β-lactamases Escherichia coli (ESBL E. coli), and MRSA/ESBL E. coli biofilm is demonstrated by a strong non-centrosymmetric near-field enhancement (NFE) effect between Met@PPS and Au nanoparticles. Furthermore, the release of metformin under near-infrared (NIR) light promotes angiogenesis and tissue repair. The results therefore show that Met@J-AuPPS exhibits excellent antibacterial/biofilm and pro-angiogenic performance, with significantly enhanced therapeutic effects in infected wounds of diabetic rat models. Conclusion: This study presents an innovative therapeutic strategy for diabetic wound infections and demonstrates that Met@J-AuPPS has potential as a multifunctional and upgradeable nanoplatform for further biomedical applications.