Direct visualization of an antidepressant analog using surface-enhanced Raman scattering in the brain

A decade of alkyne-tag Raman imaging (ATRI): applications in biological systems

“…82 An alkyne-based ratiometric SERS probe was developed and applied to monitor carbon monoxide in ex vivo tissue samples by Qin et al 117 Recently, Tanuma et al used a mimic of the antidepressant S-citalopram (S-Cit) in which a nitrile is substituted for alkyne to visualize the distribution in coronal mouse brain sections with SERS. 118 The in silico-predicted binding of alkyne-tagged S-Cit (Alk-S-Cit) to serotonin transporter was similar to that of S-Cit. Replacing nitrile with alkyne for SERS imaging did not affect brain transitivity or serotonin uptake inhibition by Alk-S-Cit.…”

“…Replacing nitrile with alkyne for SERS imaging did not affect brain transitivity or serotonin uptake inhibition by Alk- S -Cit. 118 Such strategies can help visualize the behavior of drug molecules in the original complex tissue environment, rather than just in a single cell line. While information obtained from cell lines and tissues gives great detail about the specific activity of molecules, in some cases the in vivo behavior of these molecules may be different from what we see in cell lines.…”

Raman Spectroscopy for Chemical Biology Research

“…The quantitative evaluation of the uptake speed at the single-cell level using digital SERS counting was also performed under different conditions, demonstrating the potential of alkyne-tag SERS microscopy . Alkyne-tag SERS imaging has also been successfully applied to the serotonin reuptake inhibitor S-citalopram in brain slices …”

Quantitative Drug Dynamics Visualized by Alkyne-Tagged Plasmonic-Enhanced Raman Microscopy

“…[23][24][25][26]31 Terminal alkynes show a high affinity to the surface of metals, such as silver and gold. [27][28][29][30]32,33 Therefore, strong enhancement of the Raman signal from the alkyne can be expected due to chemical adsorption onto the surface of nanoparticles. We utilized an alkyne-tagged acyloxymethyl ketone type inhibitor (Alt-AOMK), 33 an alkyne-tagged cathepsin B inhibitor, as a small-molecule drug.Three-dimensional SERS imaging was performed with home-built slit-scattering Raman microscopy, which achieves temporal resolution high enough to visualize drug uptake with the enhancement of the Raman signal.…”

“…SERS spectroscopy has been used to detect molecules at low concentrations via signal enhancement by localized plasmon resonance in metal nanoparticles. − While SERS has offered strong potential to improve the detection sensitivity and temporal resolution in live-cell imaging, , the fluctuations of both signal intensity and peak position, which are due to high sensitivity to the interaction between molecules and the metal surface, have hindered practical use of SERS in biomedical applications. , In addition, SERS peaks of small molecules may also overlap with that of endogenous molecules at the Raman fingerprint region. However, the combination of SERS and alkyne-tag can solve this issue since the unique alkyne signal can be detected separately from Raman peaks from endogenous molecules. − In our technique, gold nanoparticles introduced in live cells work as agents to report the arrival of alkyne-tagged small-molecule drugs at lysosomes, where the nanoparticles also localize during the transport. − , Terminal alkynes show a high affinity to the surface of metals, such as silver and gold. − ,, Therefore, strong enhancement of the Raman signal from the alkyne can be expected due to chemical adsorption onto the surface of nanoparticles. We utilized an alkyne-tagged acyloxymethyl ketone type inhibitor (Alt-AOMK), an alkyne-tagged cathepsin B inhibitor, as a small-molecule drug.Three-dimensional SERS imaging was performed with home-built slit-scattering Raman microscopy, which achieves temporal resolution high enough to visualize drug uptake with the enhancement of the Raman signal.…”