Magnetic and Peroxidase‐Specific Single‐Atom Nanozyme Through Cu‐Doping Engineering for Ultrasensitive and Visual Tumor Diagnosis

Abstract Designing single‐atom nanozymes (SAzymes) with superparamagnetism and peroxidase (POD)‐specific activity was still a challenge. In this research, we reported a novel magnetic SAzyme through Cu‐doping engineering in a mild one‐pot synthesis. Theoretical calculations revealed that Cu‐doping can decrease the d ‐band center of NiCu substrate so that Os atoms adsorption and agglomeration can be suppressed, single‐atom Os can absorb on the substrate, moreover, Cu‐doping can bidirectionally modulate the energy barriers in the POD (decreasing) and oxidase (OXD) (increasing) catalytic process, which endows NiCu─Os with superior POD‐activity but negligible OXD‐activity. Attributing to the superparamagnetism and superior POD‐activity, NiCu─Os SAzyme can separate targets in biological matrix and catalytic colorimetric detection without pretreatment. For practical application, NiCu─Os coupled strips were developed for point‐of‐care (POC) diagnosis of colorectal cancer (CRC), three biomarkers (CA19‐9, CEA, CST‐4) can be separated from serum and visually detected on a single strip within 20 min, achieving perfect accuracy (AUC 100%) for CRC patients’ recognition. Furthermore, attributing to the POD‐specificity, NiCu─Os enables rapid (13 min) and visual distinction of CRC tumor tissues from non‐tumor tissues via endogenous hydrogen peroxide levels. This work presents a novel paradigm for magnetic and POD‐specific SAzymes, paving the way for integrated enrichment–amplification–detection platforms in POC diagnostics.