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Cell death is a central process in developmental biology and also an important indicator of disease status and treatment efficacy. Two related fluorescent probes are described that are molecular conjugates of one or two zinc dipicolylamine (ZnDPA) coordination complexes with an appended solvatochromic benzothiazolium squaraine dye. The probes were designed to target the anionic phospholipid, phosphatidylserine (PS), that is exposed on the surface of dead and dying cells. A series of spectrometric and microscopy studies using liposomes and red blood cell ghosts as models showed that the probe with two ZnDPA targeting units produced higher affinity, stronger fluorescence “turn-on” effect, and better image contrast than the probe with one ZnDPA. Both fluorescent probes enabled “no-wash” time-lapse microscopic imaging of mammalian cell death within a culture. The probe with two ZnDPA units was used for non-invasive time-lapse imaging of cell death during the development of Xenopus laevis (frog) embryos. In vivo fluorescence micrographs revealed probe accumulation within the embryo tail, head and spine regions that were undergoing regression and apoptosis during growth and maturation. These new fluorescent probes are likely to be useful for time-resolved, non-invasive in vivo imaging of cell death process in range of living organisms. From a broader perspective, it should be possible to utilize the negative solvatochromism exhibited by benzothiazolium squaraine dyes for development of various “turn-on” deep-red fluorescent probes and materials that target cell surface biomarkers for in vitro and in vivo imaging.
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A General Strategy for Development of Near‐Infrared Fluorescent Probes for Bioimaging
Abstract Near‐infrared (NIR) fluorescent dyes with favorable photophysical properties are highly useful for bioimaging, but such dyes are still rare. The development of a unique class of NIR dyes via modifying the rhodol scaffold with fused tetrahydroquinoxaline rings is described. These new dyes showed large Stokes shifts (>110 nm). Among them, WR3, WR4, WR5, and WR6 displayed high fluorescence quantum yields and excellent photostability in aqueous solutions. Moreover, their fluorescence properties were tunable by easy modifications on the phenolic hydroxy group. Based on WR6, two NIR fluorescent turn‐on probes, WSP‐NIR and SeSP‐NIR, were devised for the detection of H2S. The probe SeSP‐NIR was applied in visualizing intracellular H2S. These dyes are expected to be useful fluorophore scaffolds in the development of new NIR probes for bioimaging.
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- Award ID(s):
- 1738305
- PAR ID:
- 10047421
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- Volume:
- 56
- Issue:
- 52
- ISSN:
- 1433-7851
- Page Range / eLocation ID:
- p. 16611-16615
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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