Zwitterionic pH-Responsive Polyurethane Nanoparticles with Cinnamaldehyde and Aggregation-Induced Emission Photosensitizers for Photodynamic Therapy of Diabetic Infected Wounds

Abstract

Diabetic infected wounds pose a significant challenge due to their refractoriness and potential for serious complications. Conventional treatment strategies primarily rely on antibiotics, which not only contribute to drug resistance but also pose risks of systemic toxicity. Photodynamic therapy (PDT) has emerged as a promising method but suffers from limited effectiveness against Gram-negative bacteria or high material toxicity. For example, quaternary ammonium salts and residual photosensitizers can produce persistent phototoxicity after the antibacterial process, exacerbating the inflammatory response in diabetic wounds and hindering tissue repair. To address these limitations, we developed an innovative zwitterionic pH-responsive polyurethane nanoparticle (PU NP) platform that integrates aggregation-induced emission (AIE) photosensitizers and cinnamaldehyde for targeted and efficient antibacterial treatment. Cinnamaldehyde is released in the bacterial infection microenvironment, synergistically enhancing ROS production with the photosensitizers under light conditions. The multifunctional nanoplatform significantly improves antibacterial efficiency while minimizing off-target toxicity, potential toxicity, and inflammatory response risks. Furthermore, the PU NP system demonstrates the ability to regulate T cell activation and migration in mouse wound tissues, thus optimizing the T cell immune microenvironment. This innovative approach holds promise for the precise treatment of diabetic infected wounds and has the potential to overcome the limitations of current photodynamic therapy, accelerating its clinical translation.