Well-defined electronic configuration cyano-bridged bimetallic nanozyme for cancer catalytic-immunotherapy.

Abstract

Heterobimetallic nanozymes hold great promising in cancer catalytic therapy by leveraging dual-active sites that are electronically coupled. However, their therapeutic potential is limited by high inherent complexity and lack of clarity regarding their electron conformation. In this study, we developed a ligand coordination field engineering strategy to construct a cyano-bridged bimetallic nanozyme Cu₂[Fe(CN)₆] (SANE) with a well-defined electronic configuration for cancer catalytic-immunotherapy. Density functional theory (DFT) calculations revealed that cyano groups, acting as strong-field bridging ligands, could form an electron delocalization network. This network, driven by electronegativity gradient of the Cu (d⁹) and Fe (d⁶) bimetallic active centers, induces synergistic distortion of d-band energy levels, which in turn enhances electron transfer and significantly improves catalytic efficiency. Furthermore, the cyano-bridging, stabilizes the structure through a strong coordination field inhibiting metal aggregation, and allowing Cu to exhibit a single-atom distribution. This further strengthens SANE catalytic therapy ability. Biomimetic modification of SANE with immunogenic tumor exosomes (iEV) enhances biocompatibility, and provides efficient Peroxidase (POD)-like and Glutathione oxidase (GSHox)-like enzymatic activities within the tumor microenvironment achieving a catalytic-immune synergistic effect. This study provides a comprehensive framework to design heterobimetallic nanozyme with ideal catalytic structure from bimetallic active sites to bridged-ligand, opening a new avenue for precisely regulating of electronic configuration in catalytic-immunotherapeutic nanoplatform.