Facilitated transport of EGFR inhibitors plays an important role in their cellular uptake

Erin L. Dunnington; Brian S. T. Wong; Ruibing Wu; Jonathan Kim; Kailun Hu; Thomas H. Ro; Dan Fu

doi:10.1117/12.2692986

13 March 2024 Facilitated transport of EGFR inhibitors plays an important role in their cellular uptake

Erin L. Dunnington, Brian S. T. Wong, Ruibing Wu, Jonathan Kim, Kailun Hu, Thomas H. Ro, Dan Fu

Proceedings Volume PC12855, Advanced Chemical Microscopy for Life Science and Translational Medicine 2024; PC128550G (2024) https://doi.org/10.1117/12.2692986
Event: SPIE BiOS, 2024, San Francisco, California, United States

Abstract

Drug resistance is influenced by molecular mechanisms that affect intracellular drug exposure and a drug’s ability to reach its protein target. Visualizing subcellular behavior of small-molecule drugs requires single-cell chemical analysis with high spatial and temporal resolution. In this work, we utilized label-free hyperspectral stimulated Raman scattering (hsSRS) microscopy to directly visualize and quantify tyrosine kinase inhibitor (TKI) drugs inside living cells. We report our live cell imaging acquisition and processing pipeline and demonstrate the capability of this hsSRS imaging method to characterize the roles of organic cation transporters (OCTs) on drug uptake. We observe significant transporter-dependent changes in intracellular drug concentration of multiple TKIs in response to the inhibition of OCTs.

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Citation Download Citation

Erin L. Dunnington, Brian S. T. Wong, Ruibing Wu, Jonathan Kim, Kailun Hu, Thomas H. Ro, and Dan Fu "Facilitated transport of EGFR inhibitors plays an important role in their cellular uptake", Proc. SPIE PC12855, Advanced Chemical Microscopy for Life Science and Translational Medicine 2024, PC128550G (13 March 2024); https://doi.org/10.1117/12.2692986

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KEYWORDS

Microscopy

Raman scattering

Live cell imaging

Lung cancer

Resistance

Visualization

Proteins

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