Abstract
Magnetic resonance imaging (MRI) is one of the most promising techniques for the non-invasive visualization of biomarkers and biologically relevant species, both in vivo and ex vivo. Although 1H MRI with paramagnetic contrast agents, such as Gd3+ complexes and iron oxide, is widely used, it often suffers from low contrast because of the large background signals caused by the abundant distribution of protons in biological samples. Here we report the use of supramolecular organic nanoparticles to detect specific proteins by 19F-based MRI in an off/on mode. In NMR spectroscopy these designed probes are silent when aggregated, but in the presence of a target protein they disassemble to produce a sharp signal. This ‘turn-on’ response allowed us to visualize clearly the protein within live cells by 19F MRI and construct an in-cell inhibitor assay. This recognition-driven disassembly of nanoprobes for a turn-on 19F signal is unprecedented and may extend the use of 19F MRI for specific protein imaging.
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Acknowledgements
We thank E. Ashihara (Kyoto University Hospital) for the blood samples, J. Miyake and T. Kunita (Kyoto University) for help with AFM and SEM measurements. Y.T. acknowledges the JSPS Research Fellowships for Young Scientists. This work was partly supported by CK integrated Medical Bio-imaging Project (MEXT) and by CREST (Japan Science and Technology Agency).
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I.H. conceived the project. Y.T., T.S., S.T. and I.H. designed the experiments. Y.T. performed all the experiments, with help from H.T. and M.S. on 19F NMR measurements. M.N. and T.M. performed the MRI experiments. The manuscript was written by Y.T., S.T. and I.H., and edited by all the co-authors.
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Takaoka, Y., Sakamoto, T., Tsukiji, S. et al. Self-assembling nanoprobes that display off/on 19F nuclear magnetic resonance signals for protein detection and imaging. Nature Chem 1, 557–561 (2009). https://doi.org/10.1038/nchem.365
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DOI: https://doi.org/10.1038/nchem.365