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

Area of Science:

• Chemical Biology
• Biomedical Imaging
• Pharmaceutical Sciences

Background:

• Visualizing live-cell drug uptake is crucial for drug development.
• Bioorthogonal imaging and Raman microscopy (including SRS) have advanced small molecule visualization.
• Current Raman microscopy methods lack sensitivity for observing low-concentration drug dynamics.

Purpose of the Study:

• To develop a highly sensitive method for real-time monitoring of small-molecule drug uptake in live cells.
• To combine alkyne-tagging with surface-enhanced Raman scattering (SERS) microscopy for enhanced detection.
• To investigate live-cell drug uptake dynamics under various conditions.

Main Methods:

• Utilized alkyne-tagged small-molecule drugs.
• Introduced gold nanoparticles into live cell lysosomes as SERS probes.
• Employed time-lapse 3D SERS imaging and digital SERS counting.
• Investigated drug uptake under different drug concentrations and temperatures.

Main Results:

• Demonstrated real-time monitoring of alkyne-tagged drug uptake in live cells using SERS microscopy.
• Achieved signal enhancement through gold nanoparticle plasmon resonance when colocalized with alkyne tags.
• Quantitatively evaluated drug uptake speed at the single-cell level.
• Showcased the technique's ability to study drug uptake under varying conditions.

Conclusions:

• Alkyne-tag SERS microscopy offers a sensitive, real-time bioorthogonal imaging approach for live-cell drug uptake studies.
• This technique has potential as an alternative to existing methods in pharmaceutical research.
• Enables detailed investigation of temporal dynamics in small-molecule drug absorption.