Peer Reviewed

1

Document Type

Article

Publication Date

3-2016

Keywords

Adenocarcinoma, Animals, Breast Neoplasms, Cell Communication, Cell Line, Tumor, Female, Fluorescent Dyes, Humans, Lysosomes, Mice, Microscopy, Fluorescence, Molecular Structure, Neoplasms, Experimental, Optical Imaging, Spectroscopy, Near-Infrared

Funder/Sponsor

D.O.S. gratefully acknowledges Science Foundation Ireland grant number 11/PI/1071(T) for financial support. E.C. and W.M.G. acknowledge the Irish Cancer Society Collaborative Cancer Research Centre BREAST-PREDICT (CCRC13GAL) for financial support. J.C.S. and A.P. acknowledge Science Foundation Ireland grant 09/IN.1/B2604 for financial support.

Comments

This article is also available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4773516/

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.

Disciplines

Chemistry | Medicinal-Pharmaceutical Chemistry | Medicine and Health Sciences

Citation

Grossi M, Morgunova M, Cheung S, Scholz D, Conroy E, Terrile M, Panarella A, Simpson JC, Gallagher WM, O'Shea DF. Lysosome triggered near-infrared fluorescence imaging of cellular trafficking processes in real time. Nature Communications. 2016;7:10855.

PubMed ID

26927507

DOI Link

10.1038/ncomms10855

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.

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