Microenvironment responsive nanozyme with photothermal effect for accelerating diabetic wound healing

Diabetic wounds (DW) are one of the most serious complications of diabetes mellitus and remain a major public health challenge, typified by an extremely complex microenvironment featuring hyperglycemia-related hypoxia, oxidative stress, endothelial dysfunction, vascular injury, and microbial invasion. Herein, a hollow mesoporous manganese dioxide (HM) nanozyme was fabricated with the template method, then loaded with berberine (BBR) and artepillin C (APC) and coated with polydopamine to form a multifunctional nanoplatform (HMBAP) for DW healing. As expected, HMBAP showed excellent antibacterial effects due to its high photothermal conversion efficiency. Additionally, HMBAP could efficiently decompose hydrogen peroxide to generate oxygen in the acidic pH environment of DW, which regulated the microenvironment and relieved local hypoxia. Meanwhile, the shell of HMBAP was also degraded by the above process, which accelerated the release of BBR and APC to achieve synergistic anti-inflammatory and glucose metabolism-promoting effects. HMBAP treatment also alleviated H₂O₂-impaired migration and tube formation in HUVECs. In a full-thickness DW model, HMBAP reduced TNF-α and hypoxia-inducible factor-1α expression and promoted collagen deposition, resulting in rapid wound closure. HMBAP also exhibited excellent biological safety due to polydopamine endowing the nanozyme with superior biocompatibility. Overall, this microenvironment responsive and photothermal nanoplatform demonstrates potential as a therapeutic agent for DW.