Optimizing p-d Orbital Hybridization of High-Entropy Nanozymes Achieving Sensitive Point-of-Care Detection of Gastric Cancer Biomarkers

Optimization of p-d orbital hybridization enhances charge interactions through increased orbital overlap, reduced electron transfer energy barriers, and regulated reaction activation energies, thereby significantly improving the catalytic kinetics. To implement the strategy, atomic substitution of Ru for Fe is employed in parent FeMnCuCoNi high-entropy nanozymes (HEzymes), yielding the RuMnCuCoNi HEzymes variant with outstanding peroxidase-like activity, demonstrating a 7-fold increase in activity over the parent alloy. Mechanistic studies reveal that the Ru 4d_<i>yz</i> orbital, as the optimal catalytic site, exhibits stronger hybridization with the p_<i>z</i> orbital of H₂O₂, which significantly enhances substrate adsorption. Concurrently, the reduced electron occupancy in antibonding orbitals strengthens orbital interactions with H₂O₂ while elevated electron density near the Fermi level accelerates electron transfer. The tripartite synergy, including enhanced adsorption, strengthened orbital interactions, and facilitated electron transfer, collectively drives the catalytic enhancement. Leveraging this nanozyme, an on-site detection platform is constructed for gastric cancer biomarkers (d-proline and d-alanine), achieving exceptional sensitivity and selectivity. Our work underscores the significance of p-d orbital hybridization regulation, providing a rational design principle for high-performance nanozymes.