title: Lysosome triggered near-infrared fluorescence imaging of cellular trafficking processes in real time.
abstract: Bioresponsive NIR-fluorophores offer the possibility for continual visualization of dynamic cellular processes with added potential for direct translation to in vivo imaging. Here we show the design, synthesis and lysosome-responsive emission properties of a new NIR fluorophore. The NIR fluorescent probe design differs from typical amine functionalized lysosomotropic stains with off/on fluorescence switching controlled by a reversible phenol/phenolate interconversion. Emission from the probe is shown to be highly selective for the lysosomes in co-imaging experiments using a HeLa cell line expressing the lysosomal-associated membrane protein 1 fused to green fluorescent protein. The responsive probe is capable of real-time continuous imaging of fundamental cellular processes such as endocytosis, lysosomal trafficking and efflux in 3D and 4D. The advantage of the NIR emission allows for direct translation to in vivo tumour imaging, which is successfully demonstrated using an MDA-MB-231 subcutaneous tumour model. This bioresponsive NIR fluorophore offers significant potential for use in live cellular and in vivo imaging, for which currently there is a deficit of suitable molecular fluorescent tools.
authors.affiliation: Department of Pharmaceutical and Medicinal Chemistry, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland.
authors.forename: Marco
authors.initials: M
authors.lastname: Grossi
authors.affiliation: Department of Pharmaceutical and Medicinal Chemistry, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland.
authors.forename: Marina
authors.initials: M
authors.lastname: Morgunova
authors.affiliation: Department of Pharmaceutical and Medicinal Chemistry, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland.|School of Chemistry and Chemical Biology, Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Shane
authors.initials: S
authors.lastname: Cheung
authors.affiliation: School of Biomolecular and Biomedical Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Dimitri
authors.initials: D
authors.lastname: Scholz
authors.affiliation: School of Biomolecular and Biomedical Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Emer
authors.initials: E
authors.lastname: Conroy
authors.affiliation: School of Biomolecular and Biomedical Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Marta
authors.initials: M
authors.lastname: Terrile
authors.affiliation: School of Biology and Environmental Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Angela
authors.initials: A
authors.lastname: Panarella
authors.affiliation: School of Biology and Environmental Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Jeremy C
authors.initials: JC
authors.lastname: Simpson
authors.affiliation: School of Biomolecular and Biomedical Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: William M
authors.initials: WM
authors.lastname: Gallagher
authors.affiliation: Department of Pharmaceutical and Medicinal Chemistry, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland.|School of Chemistry and Chemical Biology, Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Donal F
authors.initials: DF
authors.lastname: O'Shea
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism; D000818:Animals; D001943:Breast Neoplasms; D002450:Cell Communication; D045744:Cell Line, Tumor; D005260:Female; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000378:metabolism; D061848:Optical Imaging / Q000379:methods*; D019265:Spectroscopy, Near-Infrared / Q000379:methods*
chemical_list: D005456:Fluorescent Dyes