Amorphous/Crystalline Urchin-Like TiO₂ SERS Platform for Selective Recognition and Efficient Identification of Glutathione

Glutathione serves as a common biomarkers in tumor diagnosis and treatment. The levels of its intracellular concentration permit detailed investigation of the tumor microenvironment. However, low polarization and weak Raman scattering cross-section make direct and indirect Raman detection challenging. This study designs an amorphous-crystalline urchin-like TiO₂ (AC-UL-TiO₂) for the accurate identification of GSH and GSSG. By synergistically regulating the crystalline core and amorphous shell, the bandgap structure is optimized, thereby enhancing charge transfer efficiency. AC-UL-TiO₂ demonstrates excellent SERS performance in detecting dye molecules with good selectivity for mixed analytes. The enhancement factor (EF) for R6G is 6.89 × 10⁶, and the limit of detection (LOD) is 10^-10 M. A SERS-colorimetric dual-modality platform is developed based on the AC-UL-TiO₂@DTNB system to accurately monitor GSH concentrations from 0 to 1000 µM, providing a robust dual-confirmation result. Importantly, combined with the principal component analysis method, the AC-UL-TiO₂ SERS platform can directly distinguish GSH and GSSG molecules. Besides, direct SERS detection LOD for GSH and GSSG are 10^-8 M, which is 100 times higher than that of indirect detection. These findings indicate that AC-UL-TiO₂ holds potential for biomarkers trace detection in tumor microenvironments.