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

Junling Chen, Hongru Li, Qiang Wu, Tan Zhao, Haijiao Xu, Jiayin Sun, Feng Liang, Hongda Wang

Nanoscale 2021 Oct 21

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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.

Citation

Junling Chen, Hongru Li, Qiang Wu, Tan Zhao, Haijiao Xu, Jiayin Sun, Feng Liang, Hongda Wang. A multidrug-resistant P-glycoprotein assembly revealed by tariquidar-probe's super-resolution imaging. Nanoscale. 2021 Oct 21;13(40):16995-17002