Regulating Mitochondrial pH with Light and Implications for Chemoresistance. Issue 1 (10th December 2020)

• Record Type: Journal Article
• Authors: Zhao, Tinghan; Wan, Zhaoxiong; Sambath, Karthik; Yu, Shupei; Uddin, Mehrun Nahar; Zhang, Yuanwei; Belfield, Kevin D.
• Is Part Of: Chemistry. Volume 27:Issue 1(2021)
• Page Start: 247
• Page End: 251
• Publication Date: 2020-12-10
• Subjects: biosensors -- cancer -- chemoresistance -- mitochondria -- photo-triggers; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.202004278
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: 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. Abstract : Mitochondria pH regulation : A BODIPY‐based photoacid generator (BD‐PAG) exhibited mitochondria‐selective targeting. Under red‐light irradiation, BD‐PAG can release protons to decrease mitochondria pH and reduce membrane potential, which consequently promotes permeabilization of the mitochondrial membrane. Based on these properties, a combination therapy with chlorambucil indicates the potential application of BD‐PAG in anti‐chemoresistance (see figure).