Regulating Rare‐Earth Single‐Atom Nanozyme for Colorimetric‐SERS Dual‐Modal Sensing of Intracellular Glutathione

ABSTRACT Rare‐earth single‐atom nanozymes (RESAzymes) have emerged as promising catalysts due to their maximized atom utilization efficiency and tunable enzymatic activities. Herein, a colorimetric‐Surface‐enhanced Raman scattering (SERS) dual‐modal sensing platform is constructed to introduce 4f electron configurations of single‐atom ytterbium active site decorated on a nitrogen‐doped porous carbon (Yb‐N/C) by a facile hierarchical cascade‐anchoring protocol. Specifically, this unique coordination environment can promote substrate molecule adsorption and activation energy barriers, possessing excellent peroxidase (POD)‐mimicking activity and SERS enhancement performance in TMB‐H 2 O 2 system. In the presence of glutathione (GSH), Yb‐N/C catalyst is inhibited to result in reducing oxTMB for returning its colorless state, consequently diminishing both the colorimetric readout and the SERS intensity. Interestingly, this reaction mechanism from Yb‐N/C is systematically illustrated through the steady‐state kinetic, electron paramagnetic resonance (EPR), and density functional theory (DFT) calculations. Notably, the limited of detection (LOD) of GSH with colorimetric and SERS dual‐mode was as low as 0.30 and 0.11 µM, respectively. Our established dual‐modal analysis for intracellular GSH exhibits the favorable consistent with the standard kit in HepG2, KYSE150, and MCF‐7 cells, respectively. This work will offer an in‐depth understanding of RESAzymes‐mimicking activity of colorimetric‐SERS biosensors by adjusting electronic structures in carbon‐based carrier.