Starvation-protected dual-nanoplatform with antibacterial and angiogenesis properties for diabetic wound remodeling

Hyperglycemic wounds face the huge challenge of overall niche disintegration and severe healing difficulties due to blocked angiogenesis and persistent biofilm infection. Although the current reactive oxygen species (ROS) technology offers an alternative to antibiotics for diabetic wound infections, it fails to provide satisfactory long-term wound healing due to non-selective attack on normal tissues and neglect of improving blood supply. In this study, a dual-nanoplatform consisting of MoS2@GOx nanoparticles (MG NPs) and Zn single-atom nanozyme@mSiO2@GOx nanoparticles (ZSG NPs) was developed to achieve the remodeling of the diabetic wound microenvironment through the simultaneous intervention of efficient antibacterial and microvascular regeneration. Under the starvation-effect protection provided by GOx, MG NPs and ZSG NPs remained friendly to normal tissues but selectively attacked pathogenic bacteria. The MG NPs with peroxidase (POD) activity and photothermal property could generate highly toxic hydroxyl radicals (·OH) in the presence of H2O2 supplied by GOx, combining the efficient chemodynamic therapy of ZSG NPs to finally achieve the cascade amplification of ·OH production and eventual disintegration of pathogenic bacteria. The low pH provided by glucose acid induced the release of Zn2+ from ZSG NPs, directly promoting angiogenesis by upregulating the HIF-1α/VEGF signaling pathway. Moreover, this dual-nanoplatform promoted the polarization of M1 macrophages into M2 macrophages. In conclusion, the MoS2/Zn-SAN dual-nanoplatform offers a promising clinical treatment paradigm for diabetic wound healing through a multi-dimensional therapeutic strategy combining pathogen clearance, promotion of angiogenesis, and immune regulation.