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Storable, thermally activated, near-infrared chemiluminescent dyes and dye-stained microparticles for optical imaging

Nature Chemistry volume 2, pages 1025–1030 (2010)Cite this article

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Abstract

Imaging techniques are a vital part of clinical diagnostics, biomedical research and nanotechnology. Optical molecular imaging makes use of relatively harmless, low-energy light and technically straightforward instrumentation. Self-illuminating, chemiluminescent systems are particularly attractive because they have inherently high signal contrast due to the lack of background emission. Currently, chemiluminescence imaging involves short-lived molecular species that are not stored but are instead generated in situ, and they typically emit visible light, which does not penetrate far through heterogeneous biological media. Here, we describe a new paradigm for optical molecular imaging using squaraine rotaxane endoperoxides, interlocked fluorescent and chemiluminescent dye molecules that have a squaraine chromophore encapsulated inside a macrocycle endoperoxide. Squaraine rotaxane endoperoxides can be stored indefinitely at temperatures below −20 °C, but upon warming to body temperature they undergo a unimolecular chemical reaction and emit near-infrared light that can pass through a living mouse.

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Figure 1: Thermal cycloreversion of 1EP to 1 and reverse photoreaction.
Figure 2: False-colour pixel intensity maps at 38 °C with intensity scales in arbitrary units.
Figure 3: Planar chemiluminescence and reflected fluorescence from 1EP-microparticles injected subcutaneously into the dorsal side of a nude mouse rear leg at 38 °C.
Figure 4: Chemiluminescence from 1EP at 38 °C penetrates through a living nude mouse.

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Acknowledgements

The authors are grateful to the National Science Foundation (grant no. CHE 0748761 to B.D.S.) and the University of Notre Dame Integrated Imaging Facility for financial support.

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, 236 Nieuwland Science Hall, University of Notre Dame, Notre Dame, 46556, Indiana, USA

    Jeffrey M. Baumes, Jeremiah J. Gassensmith, Jay Giblin, Jung-Jae Lee, Alexander G. White, William J. Culligan, W. Matthew Leevy, Masaru Kuno & Bradley D. Smith

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Contributions

B.D.S. conceived this project and J.M.B. helped design the experiments. J.J.G., J.-J.L., W.J.C., A.G.W., W.M.L., J.G. and M.K. contributed to the experimental work and data analysis. B.D.S. and J.M.B. wrote the paper, and all co-authors contributed comments.

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Correspondence to Bradley D. Smith.

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Baumes, J., Gassensmith, J., Giblin, J. et al. Storable, thermally activated, near-infrared chemiluminescent dyes and dye-stained microparticles for optical imaging. Nature Chem 2, 1025–1030 (2010). https://doi.org/10.1038/nchem.871

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