Molecular Imprinting on Inorganic Nanozymes for Hundred-fold Enzyme Specificity

Enzyme-mimicking nanomaterials (nanozymes) are more cost-effective and robust than protein enzymes, but they lack specificity. Herein, molecularly imprinted polymers were grown on Fe₃O₄ nanozymes with peroxidase-like activity to create substrate binding pockets. Electron microscopy confirmed a shell of nanogel. By imprinting with an adsorbed substrate, moderate specificity was achieved with neutral monomers. Further introducing charged monomers led to nearly 100-fold specificity for the imprinted substrate over the nonimprinted compared to that of bare Fe₃O₄. Selective substrate binding was further confirmed by isothermal titration calorimetry. The same method was also successfully applied for imprinting on gold nanoparticles (peroxidase mimics) and nanoceria (oxidase mimics). Molecular imprinting furthers the functional enzyme mimicking aspect of nanozymes, and such hybrid materials will find applications in biosensor development, separation, environmental remediation, and drug delivery.