Janus Zn-Mo nanozymes for leveraged trienzymatic anticancer therapy

Dual-atom nanozymes (DAs) have garnered immense attention for cancer treatment due to their flexible active sites and synergistic interatomic interactions. However, precisely customizing different anionic ligands for the two active centers to disrupt their local symmetry and optimize the adsorption/desorption equilibrium of intermediates remains a major challenge. Here, we report the synthesis of Janus Zn-Mo carbon-based dual-atom nanozymes (Janus Zn-Mo DAs) bio-nanoplatform featuring Zn-N₄ and Mo-N₂O₂ motifs using a simple strategy. The Zn and Mo atoms in Janus Zn-Mo DAs are bridged by two nitrogen atoms, giving rise to an asymmetric structure that exhibits remarkable enzyme-mimicking properties. Both experimental and theoretical results revealed that the enhanced enzymatic behavior was driven by the asymmetric geometry of the diatomic sites, which shifted the d-band center of the active sites closer to the Fermi level, thereby facilitating electron transfer during the reaction. The enzyme-like catalytic activity of the Janus Zn-Mo DAs, coupled with their photothermal effect (<i>η</i> = 47.2 %), enables effective tumor growth inhibition <i>in vivo</i>, with an inhibition rate of up to 95 %. These findings provide crucial insights into the atomic- and electronic-level mechanisms of DAs with varying coordination environments and further promote the deep integration of nanotechnology and biology.