Self-stacked small molecules for ultrasensitive, substrate-free Raman imaging in vivo
Raman spectroscopy using surface-enhanced Raman scattering (SERS) nanoprobes represents an ultrasensitive and high-precision technique for in vivo imaging. Clinical translation of SERS nanoprobes has been hampered by biosafety concerns about the metal substrates used to enhance Raman signals. We report a set of small molecules with bis-thienyl-substituted benzobisthiadiazole structures that enhance Raman signal through self-stacking rather than external substrates. In our technique, called stacking-induced charge transfer-enhanced Raman scattering (SICTERS), the self-stacked small molecules form an ordered spatial arrangement that enables three-dimensional charge transfer between neighboring molecules. The Raman scattering cross-section of SICTERS nanoprobes is 1350 times higher than that of conventional SERS gold nanoprobes of similar particle size. SICTERS outperforms SERS in terms of in vivo imaging sensitivity, resolution and depth. SICTERS is capable of noninvasive Raman imaging of blood and lymphatic vasculatures, which has not been achieved by SERS. SICTERS represents an alternative technique to enhance Raman scattering for guiding the design of ultrasensitive substrate-free Raman imaging probes.
Authors
- Zeyu Xiao (ORCID: https://orcid.org/0000-0002-3457-5772)
- Hongzhuan Chen (ORCID: https://orcid.org/0000-0002-5367-2949)
- Yuanyuan Qiu (ORCID: https://orcid.org/0000-0001-8426-3796)
- Yunhui Liao (ORCID: https://orcid.org/0000-0001-7182-8372)
- Sihang Zhang (ORCID: https://orcid.org/0000-0003-1875-6896)
- Wei Lü (ORCID: https://orcid.org/0000-0002-1333-0274)
- Kai Cui (ORCID: https://orcid.org/0000-0002-6926-6830)
- Xiaohong Fang (ORCID: https://orcid.org/0000-0002-2018-0542)
- Liyang Ma (ORCID: https://orcid.org/0009-0007-8820-1403)
- Minbiao Ji (ORCID: https://orcid.org/0000-0002-9066-4008)
- Sheng Yu (ORCID: https://orcid.org/0000-0003-3837-8060)
- Yongming Zhang (ORCID: https://orcid.org/0000-0002-5664-3297)
- Shuai Gao (ORCID: https://orcid.org/0000-0003-1208-3547)
- Haoze Wang (ORCID: https://orcid.org/0000-0002-6961-6554)
Institutions
- Shanghai Jiao Tong University (CN)
- Chinese Academy of Sciences (CN)
- Fudan University (CN)
- Shanghai University of Traditional Chinese Medicine (CN)
- Ministry of Education (TH)
- Hangzhou Academy of Agricultural Sciences (CN)
- Shuguang Hospital (CN)
- State Key Laboratory of Surface Physics
Publication Details
- Journal
- Nature Biotechnology
- Published
- 2024-08-21
- DOI
- https://doi.org/10.1038/s41587-024-02342-9
- Citations
- 30
- Primary Topic
- Gold and Silver Nanoparticles Synthesis and Applications
- Type
- article
- Field-Weighted Citation Impact
- 3.54
Funders
- National Natural Science Foundation of China
- Science and Technology Commission of Shanghai Municipality
- Shanghai Municipal Health Bureau
- National Key Research and Development Program of China