“POM-Lock” nanozymes serve as chirality-keyed bacterial membrane disruptors and wound repair agents for chemodynamic therapy

Polyoxometalates (POMs) represent a class of nanomaterials distinguished by their exceptional catalytic performance and broad-spectrum antibacterial potential. However, their non-specific targeting capability often leads to collateral damage to mammalian cells, significantly constraining the precise biomedical application of POMs. Herein, employing a chiral engineering strategy, we designed and constructed chiral polyoxometalate nanozymes (D/L-POMs), which function as "POM-Lock" molecular agents capable of achieving precise targeting of bacterial membranes through a stereospecific recognition mechanism. Specifically, they were synthesized <i>via</i> a straightforward one-pot method and demonstrated superior catalytic activity, exhibiting antibacterial efficiencies exceeding 99% against both <i>E. coli</i> and <i>S. aureus</i>, significantly outperforming their achiral POM counterparts. This enhancement is attributed to the optimized W⁵⁺/W⁶⁺ redox cycling and the highly efficient membrane penetration enabled by chiral matching. Crucially, the "lock-and-key" mechanism allows L-POM to selectively disrupt bacterial membrane integrity while promoting fibroblast migration. In an infected wound model, wounds treated with L-POM achieved near-complete closure by day 10. Comprehensive biosafety evaluations revealed negligible hemolytic activity and organ toxicity. This work not only overcomes the limitation of insufficient targeting specificity in conventional POM materials but also establishes a paradigm for developing chiral nanozymes with precision antibacterial functionality.