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

Abstract

The persistent bacterial infections in diabetic-induced woundspose a significantsocietal burden,requiringinnovative antimicrobial agentsandeffectivebacteria biosensor. In thisstudy, we successfully developeda composite antimicrobial nanomaterial (Au@Zn-Tcpp/ASO-pVEC NSs)that combines acell-penetrating peptide-conjugated two-dimensional MOF with adaptive photo-responsive integration of biosensor diagnosis and therapy. Various in vitro antimicrobial experimentsdemonstrated that Au@Zn-Tcpp/ASO-pVEC NSsachieved99.99% inhibition against both E. coli and S. aureus under laser irradiation and glucose catalysis. Additionally, Au@Zn-Tcpp/ASO-pVEC NSsexhibitedsustained release of ROS and excellent photothermal properties.Furthermore, in the context of wound infections, Au@Zn-Tcpp/ASO-pVEC NSsshowed 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 throughfluorescent polypeptide probe.Overall,this antimicrobial strategy, whichcombines sensing living bacteria with a multimodal approach comprising chemodynamic therapy (CDT), photodynamic therapy (PDT), and photothermal therapy (PTT),holds substantial potential forproviding timelyclinical treatments andreliable monitoring of bacterial infections.