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

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.