Nanoconfinement-guided in situ co-deposition of single-atom cascade nanozymes combined with injectable sodium alginate hydrogels for enhanced diabetic wound healing.

Treating diabetic wounds remains a major clinical challenge due to high glucose levels, bacterial infection, insufficient oxygen supply, and oxidative stress. Herein, guided by the nanoconfinement effect, single-atom Au/Pt nanoparticles (NPs) are in situ co-deposited in mesoporous metal-organic frameworks (MOF), while synergizing with DNA aptamer (DNA-Apt) with bacterial targeting functionality and an excellent biocompatible sodium alginate hydrogel (Gel), to prepare a multifunctional bimetallic cascade nanozyme combine hydrogels (Au-Pt@ZIF-8/Apt@gel). ZIF-8 degrades in the acidic environment of a wound infection, releasing Zn2+ and Au/Pt nanoparticles, which produce reactive oxygen species (ROS) under the catalysis of glucose to inactivate bacteria. Notably, Au-Pt@ZIF-8 nanozymes depositing Au/Pt nanoparticles exhibit a nanoconfinement effect that enhances the cascade nanozymes activity, which is about 2-3 times higher than that of monoconfined or nonconfined nanozyme. In addition, in vitro bacteriostatic tests show the nanozymes have broad-spectrum antimicrobial effects, with better inhibition of Gram-positive than negative bacteria. In vivo experiments indicate that Au-Pt@ZIF-8/Apt@gel has satisfactory antibacterial efficacy in both normal and diabetic mice, as well as optimal skin wound healing ability and significant reduction of inflammation in infected wounds. Consequently, the proposed system holds great potential for developing integrated nanoplatforms for on-demand treatment of bacterial-infected diabetic wounds.