Surface-enhanced Raman spectroscopy (SERS) technology has unique advantages in the diagnosis and biological imaging. The current SERS bioprobe has been limited to noble metal nanomaterials. However, the non-selective enhancement characteristics of noble metal nanomaterials in SERS applications have limited their application such as biological diagnosis and treatment. Therefore, it is an urgent to develop a non-metal SERS bioprobe with high SERS enhancement factors for tumor imaging and diagnosis.
Based on the excellent biocompatibility, structural stability and selective enhancement characteristics of metal oxides, the Nano Biomaterials Research Team of Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences has constructed amorphous-crystalline core-shell TiO2 nanoparticles as SERS substrate, the crystal core structure is an electron-rich system, which can provide electron for the amorphous shell. The surface energy level of the amorphous surface and the orbital energy level of the target molecule have a strong coupling effect, which makes photo-induced electrons transferred from the crystal core to the amorphous shell. The electrons in shell and target molecules are effectively transported and transferred, thereby improving the photo-induced charge transfer efficiency of the semiconductor-molecule SERS system, endowing excellent SERS enhancement factor of 105, which can achieve single-cell SERS spectrum detection and imaging requirements. The biological SERS probe is built by amorphous-crystalline core-shell structure TiO2 nanoparticles, Raman signal molecule, biomacromolecules and folate antibodies, which can quickly identify breast cancer cells and drug-resistant breast cancer cells. And drug-resistant breast cancer cells are successfully killed through the photothermal properties of amorphous-crystalline core-shell structure TiO2 nanoparticles, thereby achieving the effect of accurate diagnosis and treatment of drug-resistant breast cancer cells. The construction of the semiconductor-based biological SERS probe not only widens the practical application range of SERS technology, but also shows good application value in the field of biological imaging, diagnosis, and treatment. Relevant research results were published in ACS Appl. Mater. Interfaces, 2020, 12, 4204 (cover), and applied for invention patent 201911014528.3. The above work has been supported by the National Natural Science Foundation of China, the National Precision Research, Development Program "Precision Medical Research", China Postdoctoral Natural Science Foundation, and Zhejiang Province, and Ningbo.
Figure 1 Synthesis pathway of core-shell TiO2 nanoparticle biological SERS probe and application in targeted imaging of drug-resistant breast cancer cells.