Light-responsive Au@Zn-TCPP nanozyme functionalized with cell-penetrating peptide and antisense oligonucleotide for sensing living bacteria and synergistic therapy of diabetic wounds

The persistent bacterial infections in diabetic-induced wounds pose a significant societal burden, requiring innovative antimicrobial agents and effective bacteria biosensor. In this study, we successfully developed a composite antimicrobial nanomaterial (Au@Zn-Tcpp/ASO-pVEC NSs) that combines a cell-penetrating peptide-conjugated two-dimensional MOF with adaptive photo-responsive integration of biosensor diagnosis and therapy. Various in vitro antimicrobial experiments demonstrated that Au@Zn-Tcpp/ASO-pVEC NSs achieved 99.99% inhibition against both E. coli and S. aureus under laser irradiation and glucose catalysis. Additionally, Au@Zn-Tcpp/ASO-pVEC NSs exhibited sustained release of ROS and excellent photothermal properties. Furthermore, in the context of wound infections, Au@Zn-Tcpp/ASO-pVEC NSs showed optimal skin wound healing, with less than 2% residual infected area against diabetic bacterial infections and significantly reduced inflammation. Moreover, these nanomaterials demonstrated the capability to effectively detect bacteria through fluorescent polypeptide probe. Overall, this antimicrobial strategy, which combines sensing living bacteria with a multimodal approach comprising chemodynamic therapy (CDT), photodynamic therapy (PDT), and photothermal therapy (PTT), holds substantial potential for providing timely clinical treatments and reliable monitoring of bacterial infections.