A DNA nanostructure-enabled photothermal hydrogel for synergistic antibacterial therapy and infected wound repair.

Abstract

Bacterial infection is a major cause of delayed wound healing, while overuse of antibiotics has accelerated the emergence of antimicrobial resistance. Developing multifunctional antibacterial biomaterials that eradicate bacteria without relying on conventional antibiotics is therefore highly desirable. Herein, we report an injectable polyethylene glycol (PEG)-based hydrogel incorporating gold nanorods (ARs) and a DNA nanostructure-mediated silver and antisense oligonucleotide delivery system (A-C@Ag) to achieve synergistic antibacterial therapy and enhanced skin regeneration. The hydrogel is formed by rapid thiol-maleimide crosslinking of PEG precursors containing AR@A-C@Ag, providing excellent injectability, biocompatibility, and mechanical stability. Upon near-infrared irradiation, the AR generates mild photothermal heating to directly damage bacteria and simultaneously promotes the on-demand release of Ag+ and antisense oligonucleotides from the DNA nanostructure, resulting in markedly enhanced antibacterial activity against both Staphylococcus aureus and Escherichia coli by facilitating bacterial membrane disruption. In a S. aureus-infected full-thickness wound model, AR@A-C@Ag/Gel under NIR irradiation significantly accelerated wound closure by efficiently eliminating bacteria, suppressing inflammation, promoting angiogenesis and collagen deposition, and facilitating the regeneration of skin appendages. This work demonstrates that integrating DNA nanostructure-enabled drug delivery with mild photothermal therapy represents an effective strategy for constructing antibiotic-free antibacterial hydrogels for infected wound repair.