NIR-triggered and glucose-powered hollow mesoporous Mo-based single-atom nanozymes for cascade chemodynamic diabetic infection therapy

Diabetic infections/wounds remain to be a threatening challenge as it seriously leads to lower limb amputation with endless pains and subsequent high economic/psychosocial costs. The exceptional peroxidase-like activity of single-atom nanozymes (SAzymes) holds great promise for chemodynamic therapy (CDT) of diabetic infection, but is extremely restricted by the near-neutral pH and insufficient H₂O₂ levels in physiological conditions. Herein, we innovated a hollow mesoporous molybdenum single-atom nanozyme (HMMo-zyme) featured with catalytic activity, photothermal performance and drug delivery properties for more effective antibacterial therapeutic in diabetic conditions. The glucose oxidase (GOx) was encapsulated into HMMo-zyme with phase-change material (PCM) to form HMMo/GOx@P system, which could be controllably disassembled by near-infrared ray (NIR) to trigger cascade CDT toward bacterial infections. The results revealed that the release of GOx accelerated by NIR could facilitate the continuous conversion of glucose (Glu) into gluconic acid, accompanied by a sharply decrease in pH to establish a low-pH environment that notably enhanced the catalytic activity of HMMo-zyme, which subsequently drives the conversion of generated H₂O₂ into toxic hydroxyl radicals (<b>·</b>OH) for amplified anti-bacterial treatment. As a proof of the concept, this NIR-assisted HMMo/GOx@P strategy could efficiently inhibit/kill bacteria and suppress tissue inflammations, thereby accelerating the wound healing processes both in <i>in vitro</i> and <i>in vivo</i> diabetic infection models. This study provides a novel strategy that may serve as a promising alternative for antibiotic therapeutics against diabetic infection, thus holding promise for more effective diabetic infection treatment manipulating Mo-based SAzymes.