Issue 39, 2023

Chemical biology fluorescent tools for in vitro investigation of the multidrug resistant P-glycoprotein (P-gp) expression in tumor cells

Abstract

Selective P-glycoprotein (P-gp)-targeted fluorescent conjugates are desirable tools to investigate the role of P-gp, a protein strongly implicated in mediating multidrug resistance and a major cause of chemotherapy failure. Herein, we report the development of 25 novel fluorescent small-molecule conjugates with varying physicochemical and optical properties, and their biological evaluation in a cell model as P-gp targeted constructs. This investigation revealed relationships between molecular structure and cell behavior and uncovered the capacity of conjugates with varying fluorophores to selectively target P-gp. Sulfocyanine 3 labeled conjugates (5, 10, 24, 29, 34) showed a particular intracellular staining pattern. Other conjugates bearing a boron dipyrromethene (BODIPY) core (3, 8, 13, 22, 27 (BODIPY FL), 12 (BODIPY 564/570) and 4, 9 (BODIPY 650/665)) or a 7-nitrobenz-2-oxa-1,3-diazole (NBD) core (11, 30) showed potential for global P-gp direct detection and quantification. These fluorescent conjugates holds key advantages over existing methods for drug resistance evaluation with regards to P-gp expression and could be used as innovative tools in preclinical assays and clinical diagnosis.

Graphical abstract: Chemical biology fluorescent tools for in vitro investigation of the multidrug resistant P-glycoprotein (P-gp) expression in tumor cells

Supplementary files

Article information

Article type
Paper
Submitted
27 Jul 2023
Accepted
02 Sep 2023
First published
08 Sep 2023
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2023,13, 27016-27035

Chemical biology fluorescent tools for in vitro investigation of the multidrug resistant P-glycoprotein (P-gp) expression in tumor cells

P. Daumar, A. Goisnard, C. Dubois, M. Roux, M. Depresle, F. Penault-Llorca, M. Bamdad and E. Mounetou, RSC Adv., 2023, 13, 27016 DOI: 10.1039/D3RA05093A

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