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一种用于成像铁死亡和线粒体自噬的多功能线粒体近红外探针。

A multipurpose mitochondrial NIR probe for imaging ferroptosis and mitophagy.

机构信息

Department of Chemistry, Indian Institute of Technology, Gandhinagar, Palaj, Gandhinagar 382355, Gujarat, India.

Department of Biological Engineering, Indian Institute of Technology, Gandhinagar 382355, India.

出版信息

J Mater Chem B. 2024 May 15;12(19):4698-4707. doi: 10.1039/d4tb00293h.

DOI:10.1039/d4tb00293h
PMID:38652007
Abstract

This paper explores the use of a di-cationic fluorophore for visualizing mitochondria in live cells independent of membrane potential. Through the synthesized di-cationic fluorophore, we investigate the monitoring of viscosity, ferroptosis, stress-induced mitophagy, and lysosomal uptake of damaged mitochondria. The designed fluorophore is based on DQAsomes, cationic vesicles responsible for transporting drugs and DNA to mitochondria. The symmetric fluorophores possess two charge centres separated by an alkyl chain and are distinguished by a pyridinium group for mitochondrial selectivity, the C-12 alkyl substitution for membrane affinity, and an electron donor-π-acceptor fluorescent scaffold for intramolecular charge transfer. The synthesized fluorophores, PP and NP, emit wavelengths exceeding 600 nm, with a significant Stokes shift (130-211 nm), and NP demonstrates near-infrared emission (∼690 nm). Our study underscores the potential of these fluorophores for live-cell imaging, examining physiological responses such as viscosity and ferroptosis, and highlights their utility in investigating mitophagy damage and lysosomal uptake.

摘要

本文探讨了一种双阳离子荧光染料在独立于膜电位的情况下用于可视化活细胞中线粒体的用途。通过合成的双阳离子荧光染料,我们研究了监测粘度、铁死亡、应激诱导的线粒体自噬以及受损线粒体的溶酶体摄取。所设计的荧光染料基于 DQAsomes,即负责将药物和 DNA 递送到线粒体的阳离子囊泡。对称的荧光染料具有两个电荷中心,由烷基链隔开,并通过吡啶基团区分,以实现线粒体选择性,C-12 烷基取代以提高膜亲和力,以及电子给体-π-受体荧光骨架以实现分子内电荷转移。合成的荧光染料 PP 和 NP 发射波长超过 600nm,具有显著的斯托克斯位移(130-211nm),而 NP 则表现出近红外发射(∼690nm)。我们的研究强调了这些荧光染料在活细胞成像中的潜力,可用于检查粘度和铁死亡等生理反应,并突出了它们在研究线粒体自噬损伤和溶酶体摄取方面的应用。

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