Quantitative drug dynamics visualized by alkyne-tagged plasmonic-enhanced Raman microscopy

Kota Koike, Kazuki Bando, Jun Ando, Hiroyuki Yamakoshi, Naoki Terayama, Kosuke Dodo, Nicholas Isaac Smith, Mikiko Sodeoka, Katsumasa Fujita

研究成果: Article査読

21 被引用数 (Scopus)


Visualizing live-cell uptake of small-molecule drugs is paramount for drug development and pharmaceutical sciences. Bioorthogonal imaging with click chemistry has made significant contributions to the field, visualizing small molecules in cells. Furthermore, recent developments in Raman microscopy, including stimulated Raman scattering (SRS) microscopy, have realized direct visualization of alkyne-tagged small-molecule drugs in live cells. However, Raman and SRS microscopy still suffer from limited detection sensitivity with low concentration molecules for observing temporal dynamics of drug uptake. Here, we demonstrate the combination of alkyne-tag and surface-enhanced Raman scattering (SERS) microscopy for the real-time monitoring of drug uptake in live cells. Gold nanoparticles are introduced into lysosomes of live cells by endocytosis and work as SERS probes. Raman signals of alkynes can be boosted by enhanced electric fields generated by plasmon resonance of gold nanoparticles when alkyne-tagged small molecules are colocalized with the nanoparticles. With time-lapse 3D SERS imaging, this technique allows us to investigate drug uptake by live cells with different chemical and physical conditions. We also perform quantitative evaluation of the uptake speed at the single-cell level using digital SERS counting under different quantities of drug molecules and temperature conditions. Our results illustrate that alkyne-tag SERS microscopy has a potential to be an alternative bioorthogonal imaging technique to investigate temporal dynamics of small-molecule uptake of live cells for pharmaceutical research.

ジャーナルACS Nano
出版ステータスPublished - 2020 11月 24

ASJC Scopus subject areas

  • 材料科学(全般)
  • 工学(全般)
  • 物理学および天文学(全般)


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