Abstract
Nanozymes, exemplified by metal nanoparticles, have shown promise in the fields of biological diagnostics and therapeutics. However, their practical application is often hindered by aggregation or deactivation in complex biological systems. Here, we develop a DNA-engineered nanozyme coating to preserve the peroxidase-like catalytic activity of platinum nanoparticles in complex biological environments. We employed thiol-modified single-stranded DNA to coat the platinum nanoparticles through metal-sulfur interaction. We found that the negatively charged DNA coating prevents the aggregation of platinum nanoparticles in high-salt environments. Moreover, the DNA coating functions as a molecular sieve, inhibiting non-specific protein adsorption while preserving substrate access to the catalytic interface, thus sustaining high peroxidase-like catalytic activity in serum. As a proof of concept, we demonstrate miRNA detection in serum samples with a detection limit of 1 fM. This approach offers a versatile strategy for molecular diagnostics of nanozymes in complex biological environments.