New-Typed Co₃O₄@Co–Fe Oxide/AuNPs Double Nanoboxes Nanozyme Enables Bimodal Monitoring Metallothioneins

Metallothioneins (MTs) are important biomarkers for the early diagnosis of malignancies. However, traditional assay methods for MTs heavily rely on single-mode detection, which is confronted with enduring challenges in low cost-effectiveness and relatively poor accuracy in a complex matrix. Herein, we design a new-typed Co₃O₄@Co-Fe oxide/AuNPs double nanoboxes (DNBs) nanozyme for constructing colorimetric-SERS bimodal sensor to monitor MTs. Specifically, the prepared Co₃O₄@Co-Fe oxide/AuNPs DNBs nanozyme demonstrates remarkably enhanced peroxidase-like (POD-like) activity and high SERS activity, which catalyze the decomposition of H₂O₂ to generate hydroxyl radicals that promote the conversion of colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue ox-TMB with SERS activity. Taking advantage of the free radical scavenging effect of MTs, the colorimetric-SERS dual-readout signals are first achieved for the quantitative detection of MTs. The constructed bimodal sensor shows wide linear ranges of 0.1-1000 μM (colorimetric) and 0.0005-400 μM (SERS) for MTs, and the detection limits are as low as 0.031 μM (colorimetric) and 0.037 nM (SERS). Besides, the bimodal MTs sensor possesses excellent specificity as well as reliable practicality for MTs in human serum. This research offers an insight into design versatile nanozymes for the development of bimodal sensing for MTs, which can be expanded to various biosensing fields.