A Highly Sensitive SERS Platform Based on Small-Sized Ag/GQDs Nanozyme for Intracellular Analysis

Abstract The small-sized plasmonic nanoparticles are easily internalized by cells and organelles, but usually possess poor surface-enhanced Raman scattering (SERS) activity, restricting their promising applications for intracellular SERS analysis. To break the current bottleneck of intracellular SERS application, herein, a uniform and small-sized (ca. 10 nm) core-shell Ag/oxidized graphene quantum dots (o-GQDs) nanohybrids have been prepared. The Ag/o-GQDs inherit unique features with parallel-interlaced stacking of o-GQDs as capping agent, possess the increasing and broadening plasmon adsorption and display a unique edge state charge transfer (CT) resonance in the long-wavelength region of visible light, enabling the enhanced electromagnetic (EM) and CT effect for superior SERS sensitivity at lower energy. Further, the Ag/o-GQDs demonstrate excellent biocompatibility and highly efficient nanozymatically catalytic activity, which are first put forward to integrate efficient SERS with Ag/o-GQDs nanozyme to catalyze peroxidase-like reaction for accurate sensing of the intracellular H2O2 at the subcellular level. Moreover, the Ag/o-GQDs nanozyme-catalyzed reactive oxygen species (ROS) generation and the cancer cell multisubcellular-targeting capability provide a promising strategy for the synergistically catalytic therapy specifically toward tumors. This study illustrates a significant route to design an efficient small-sized noble metal/carbon nanozymatic SERS substrate, and demonstrates an exciting potential for ultrasensitive SERS bioanalysis at the subcellular level.