A multidrug-resistant P-glycoprotein assembly revealed by tariquidar-probe's super-resolution imaging. Issue 40 (7th October 2021)

• Record Type: Journal Article
• Authors: Chen, Junling; Li, Hongru; Wu, Qiang; Zhao, Tan; Xu, Haijiao; Sun, Jiayin; Liang, Feng; Wang, Hongda
• Is Part Of: Nanoscale. Volume 13:Issue 40(2021)
• Page Start: 16995
• Page End: 17002
• Publication Date: 2021-10-07
• Subjects: Nanoscience -- Periodicals; Nanotechnology -- Periodicals; 620.505
• DOI: 10.1039/d1nr03980f
• Languages: English
• ISSNs: 2040-3364

Abstract

Abstract : The development of small-molecule fluorescent probes for p-glycoproteins is helpful to study their drug resistance mechanism. 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.