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Regulating Mitochondrial pH with Light and Implications for Chemoresistance
Author(s) -
Zhao Tinghan,
Wan Zhaoxiong,
Sambath Karthik,
Yu Shupei,
Uddin Mehrun Nahar,
Zhang Yuanwei,
Belfield Kevin D.
Publication year - 2021
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202004278
Subject(s) - mitochondrion , depolarization , apoptosis , inner mitochondrial membrane , membrane potential , viability assay , microbiology and biotechnology , chemistry , biophysics , cell , bodipy , biology , biochemistry , fluorescence , physics , quantum mechanics
Chemoresistance is one of the major challenges for cancer treatment, more recently ascribed to defective mitochondrial outer membrane permeabilization (MOMP), significantly diminishing chemotherapeutic agent‐induced apoptosis. A boron‐dipyrromethene (BODIPY) chromophore‐based triarylsulfonium photoacid generator (BD‐PAG) was used to target mitochondria with the aim to regulate mitochondrial pH and further depolarize the mitochondrial membrane. Cell viability assays demonstrated the relative biocompatibility of BD‐PAG in the dark while live cell imaging suggested high accumulation in mitochondria. Specific assays indicated that BD‐PAG is capable of regulating mitochondrial pH with significant effects on mitochondrial membrane depolarization. Therapeutic tests using chlorambucil in combination with BD‐PAG revealed a new strategy in chemoresistance suppression.