Amorphous Nitrogen-Doped Carbon Nanocages with Excellent SERS Sensitivity and Stability for Accurate Identification of Tumor Cells

The surface-enhanced Raman scattering (SERS) bioprobe's strategy for identifying tumor cells always depended on the intensity difference of the Raman signal compared with that of normal cells. Hence, exploring novel SERS nanostructure with excellent spectra stability, a high enhancement factor (EF), and good biocompatibility is a primary premise for boosting SERS signal reliability and accuracy of tumor cells. Here, high SERS EF (5.52 × 10⁶) is acquired by developing novel amorphous nitrogen-doped carbon (NDC) nanocages (NCs), whose EF value was in a leading position among carbon-based SERS substrates. In addition, a uniform SERS signal was obtained on NDC NCs due to homogeneous morphology and size. The delocalized carbon-conjugated systems of graphitic-N, pyrrole-N, and pyridine-N with lone pair electrons increase the electronic density of states and reduce the electron localization function of NDC NCs, thereby promoting the charge transfer process. The electron-donor platform of the NDC NCs facilitates the thermodynamic process of charge transfer, resulting in multimode vibrational coupling in the surface complexes, which greatly amplifies the molecular polarizability. Importantly, the good biocompatibility and signal stability endow these NDC NC SERS bioprobes unique superiority in distinguishing tumor cells, and quantitative recognition of two triple-negative breast cancer cells based on SERS detection mode has been successfully realized.