Theranostics 2020; 10(5):2067-2094. doi:10.7150/thno.39968 This issue


Gap-enhanced Raman tags: fabrication, optical properties, and theranostic applications

Nikolai G. Khlebtsov1,2,✉, Li Lin3, Boris N. Khlebtsov1, Jian Ye3,4,5,✉

1. Institute of Biochemistry and Physiology of Plants and Microorganisms, Russian Academy of Sciences, 13 Prospekt Entuziastov, Saratov 410049, Russia
2. Saratov National Research State University, 83 Ulitsa Astrakhanskaya, Saratov 410026, Russia
3. State Key Laboratory of Oncogenes and Related Genes, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, P. R. China
4. Department of Nuclear Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, P.R. China
5. Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P. R. China

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Khlebtsov NG, Lin L, Khlebtsov BN, Ye J. Gap-enhanced Raman tags: fabrication, optical properties, and theranostic applications. Theranostics 2020; 10(5):2067-2094. doi:10.7150/thno.39968. Available from

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Graphic abstract

Gap-enhanced Raman tags (GERTs) are emerging probes of surface-enhanced Raman scattering (SERS) spectroscopy that have found promising analytical, bioimaging, and theranostic applications. Because of their internal location, Raman reporter molecules are protected from unwanted external environments and particle aggregation and demonstrate superior SERS responses owing to the strongly enhanced electromagnetic fields in the gaps between metal core-shell structures. In this review, we discuss recent progress in the synthesis, simulation, and experimental studies of the optical properties and biomedical applications of novel spherically symmetrical and anisotropic GERTs fabricated with common plasmonic metals—gold (Au) and silver (Ag). Our discussion is focused on the design and synthetic strategies that ensure the optimal parameters and highest enhancement factors of GERTs for sensing and theranostics. In particular, we consider various core-shell structures with build-in nanogaps to explain why they would benefit the plasmonic GERTs as a superior SERS tag and how this would help future research in clinical analytics and therapeutics.

Keywords: surface-enhanced Raman scattering (SERS), gap-enhanced Raman tags (GERTS), plasmonic core-shell nanoparticles, bioimaging, plasmonic photothermal therapy, theranostics