Reactive Oxygen-Correlated Photothermal Imaging of Smart COF Nanoreactors for Monitoring Chemodynamic Sterilization and Promoting Wound Healing.

ABSTRACT

Chemodynamic therapy (CDT) has emerged as a promising approach for treating infected diabetic wounds, while reliable imaging technology for simultaneous monitoring of ROS and therapeutic processes is still a formidable challenge. Herein, smart covalent organic framework (COF) nanoreactors (COF NRs) are constructed by hyaluronic acid (HA) packaged glucose oxidase (GOx) covalently linked Fe-COF for diabetic wound healing. Upon the breakdown of the HA protective layer, GOx consumes glucose to produce gluconic acid and hydrogen peroxide (H2O2), resulting in decreased local pH and H2O2 supplementation. Density functional theory (DFT) calculations show that Fe-COF has high catalytic activity towards H2O2, leading to in situ generation of hydroxyl radicals (·OH) for sterilization, and the localized downregulation of glucose effectively improved the microenvironment of diabetic wounds. Meanwhile, based on the near-infrared photothermal imaging of oxidized 3,3',5,5'-tetramethylbenzidine (oxTMB), the authors showed that TMB can be applied for the point-of-care testing of ·OH and glucose, and assessing the sterilization progress in vivo. More significantly, the facile photothermal signaling strategy can be extended to monitor various ROS-mediated therapeutic systems, enabling accurate prediction of treatment outcomes.