Multifunctional Nanomedicine with Microenvironment-Regulated Controlled Release for Promoting Healing of Infected Diabetic Wounds

Diabetic wounds pose an ongoing challenge due to their difficult healing and complex microenvironmental nature, and the presence of bacterial infections significantly exacerbates this issue. Here, leveraging the characteristics of the bacterial infection microenvironment, we developed a nanomedicine based on a hollow covalent organic framework (HCOF) for the synergistic application of chemodynamic therapy (CDT) and photodynamic therapy (PDT) in antimicrobial treatment. With HCOF as the carrier, photosensitizer Chlorin e6 (Ce6) is loaded by electrostatic adsorption, and then a manganese dioxide (MnO2) nanoshell was grown on the Ce6@HCOF surface to obtain Ce6@HCOF@MnO2. The nanomedicine exhibits a glutathione (GSH) stimulus response, thereby releasing Mn2+ and Ce6. Mn2+ engages in a Fenton-like reaction with the naturally occurring hydrogen peroxide (H2O2) at the wound site, resulting in the production of highly reactive hydroxyl radicals, while Ce6 generates singlet oxygen under laser irradiation, thus achieving CDT/PDT dual-mode synergistic therapy. Notably, Ce6@HCOF@MnO2 has not only demonstrated the ability to promote collagen deposition but also accelerated skin regeneration and aided in the repair of diabetic wounds. This pioneering approach possesses significant potential for the multifaceted management of bacterial infections and the diseases they precipitate.