Abstract: Since nanozymes typically exhibit excellent peroxidase-like activity under acidic conditions, while the most natural enzymes achieve optimal catalytic activity near neutral pH, this mismatch between operational conditions has limited the development and application of nanozyme–natural enzyme cascade sensing systems. In this study, Fe-based metal-organic frameworks (MOFs) were selected as nanozymes, and Fe-MIL-88 with various morphologies and sizes were synthesized via solvent modulation, among which the concave octahedral Fe-MIL-88-c showed higher peroxidase-like activity. Furthermore, by the surface charge regulation of Fe-MIL-88-c using by aspartic acid (Asp), the negative surface charge density was significantly enhanced, enabling Asp-Fe-MIL-88-c to display outstanding peroxidase-like activity under neutral conditions. Particularly, its activity was 44 times higher than that of Fe-MIL-88-c at pH 7.0. Through a cascade reaction between Asp-Fe-MIL-88-c and D-amino acid oxidase, a one-pot rapid colorimetric detection of D-amino acids, a gastric cancer biomarker, in saliva was developed. Additionally, integration with smartphone further enabled highly convenient detection of it. This work provides a new tool for highly sensitive and fast detection of D-amino acids and offers novel insights into designing nanozymes with high activity under neutral conditions.

Key words: Fe-MIL-88, D-amino acid, Peroxidase-like nanozyme, Aspartic acid, Neutral pH