Regulating Mitochondrial pH with Light and Implications for Chemoresistance

Tinghan Zhao, Zhaoxiong Wan, Karthik Sambath, Shupei Yu, Mehrun Nahar Uddin, Yuanwei Zhang, Kevin D. Belfield

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)247-251
Number of pages5
JournalChemistry - A European Journal
Volume27
Issue number1
DOIs
StatePublished - Jan 4 2021

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Organic Chemistry

Keywords

  • biosensors
  • cancer
  • chemoresistance
  • mitochondria
  • photo-triggers

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