Issue 40, 2021

A multidrug-resistant P-glycoprotein assembly revealed by tariquidar-probe's super-resolution imaging

Abstract

As an efflux pump, P-glycoproteins (P-gps) are over-expressed in many cancer cell types to confer them with multi-drug resistance. Many studies have focused on elucidating their molecular structure or protein expression; however, the relationship between the molecular assembly and dysfunction remains unclear. Super-resolution microscope is an excellent imaging tool to reveal the molecular biological details, but its high-quality imaging often suffers from the labeling method currently available. In this work, by exploiting its specificity and small size, tariquidar (specific inhibitor of P-gp) was modified by TAMRA to form a small chemical probe of P-gp. By direct stochastic optical reconstruction microscopic (dSTORM) imaging, tariquidar-TAMRA was first revealed to possess a higher labeling superiority and high binding specificity. Then, with the application of tariquidar-TAMRA labeling, we found that P-gps accumulate into larger and denser clusters on cancer cells and drug-resistant cells than on normal cells and drug-sensitive cells, indicating that P-gps can facilitate the pumping efficiency by aggregating together to form functional platforms. Moreover, these specific distribution patterns might serve as potential biomarkers for tumor and drug therapy screening.

Graphical abstract: A multidrug-resistant P-glycoprotein assembly revealed by tariquidar-probe's super-resolution imaging

Supplementary files

Article information

Article type
Paper
Submitted
19 Jun 2021
Accepted
07 Sep 2021
First published
25 Sep 2021

Nanoscale, 2021,13, 16995-17002

A multidrug-resistant P-glycoprotein assembly revealed by tariquidar-probe's super-resolution imaging

J. Chen, H. Li, Q. Wu, T. Zhao, H. Xu, J. Sun, F. Liang and H. Wang, Nanoscale, 2021, 13, 16995 DOI: 10.1039/D1NR03980F

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