Real-time fluorescence diagnosis guided glucose-triggered chemodynamic therapy for diabetic wounds using covalent organic framework@metal-organic framework cascade nanoreactor

Diabetic wound management remains a major clinical challenge due to the difficulty in achieving precise therapeutic modulation and the lack of reliable approaches for real-time identification of wound pathological stages. To address this, we report the development of a novel covalent organic frameworks@metal-organic frameworks theranostic nanoreactor, namely glucose oxidase (GOx)-encapsulated zeolitic imidazolate framework-8 (ZIF-8) assembled on the surface of fluorescent hollow covalent organic frameworks (denoted as HCOF@FZG) through a one-pot coordination strategy. The nanoreactor is designed to concurrently monitor wound pH fluctuations and provide synergistic treatment for diabetic wounds. Leveraging pH-triggered fluorescence changes, HCOF@FZG enables non-invasive, dynamic assessment of wound conditions, allowing for precise discrimination between the healing and infection stages. Upon detecting signs of infection, HCOF@FZG initiates a cascade reaction in which GOx-mediated oxidation depletes local glucose for starvation therapy, while the generated H 2 O 2 is subsequently converted into bactericidal hydroxyl radicals via a Fenton-like reaction for chemodynamic therapy. Moreover, HCOF@FZG demonstrates remarkable pro-healing properties by significantly promoting endothelial cell proliferation and migration. This acceleration of granulation tissue formation and re-epithelialization critically improves overall wound recovery, offering an intelligent and precise solution for managing diabetic chronic wounds.