Department of Chemistry and Environmental Science, New Jersey Institute of Technology, 323 Martin Luther King Jr. Blvd., Newark, New Jersey, 07102, USA.
Chemistry. 2021 Jan 4;27(1):247-251. doi: 10.1002/chem.202004278. Epub 2020 Dec 10.
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.
化学耐药性是癌症治疗的主要挑战之一，最近归因于线粒体外膜通透性缺陷（MOMP），显著降低了化疗药物诱导的细胞凋亡。一种基于硼二吡咯甲川（BODIPY）发色团的三芳基硫鎓光酸产生剂（BD-PAG）被用于靶向线粒体，旨在调节线粒体 pH 值并进一步去极化线粒体膜。细胞活力测定表明，BD-PAG 在黑暗中具有相对的生物相容性，而活细胞成像表明其在线粒体中高度积累。特定的测定表明，BD-PAG 能够调节线粒体 pH 值，并对线粒体膜去极化产生显著影响。使用苯丁酸氮芥与 BD-PAG 联合进行的治疗测试揭示了一种抑制化学耐药性的新策略。
