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Distance-dependent magnetic resonance tuning as a versatile MRI sensing platform for biological targets

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Abstract

Nanoscale distance-dependent phenomena, such as Förster resonance energy transfer, are important interactions for use in sensing and imaging, but their versatility for bioimaging can be limited by undesirable photon interactions with the surrounding biological matrix, especially in in vivo systems1,2,3,4. Here, we report a new type of magnetism-based nanoscale distance-dependent phenomenon that can quantitatively and reversibly sense and image intra-/intermolecular interactions of biologically important targets. We introduce distance-dependent magnetic resonance tuning (MRET), which occurs between a paramagnetic ‘enhancer’ and a superparamagnetic ‘quencher’, where the T1 magnetic resonance imaging (MRI) signal is tuned ON or OFF depending on the separation distance between the quencher and the enhancer. With MRET, we demonstrate the principle of an MRI-based ruler for nanometre-scale distance measurement and the successful detection of both molecular interactions (for example, cleavage, binding, folding and unfolding) and biological targets in in vitro and in vivo systems. MRET can serve as a novel sensing principle to augment the exploration of a wide range of biological systems.

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Figure 1: Schematic representation of distance-dependent magnetic resonance tuning.
Figure 2: Distance dependence of MRET and resulting variation in the T1 MRI relaxation.
Figure 3: MRET sensor for recognizing molecular interactions.
Figure 4: MRET probe for matrix metalloproteinase-2.

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Acknowledgements

This work was supported by the Institute for Basic Science (IBS-R026-D1). We thank P. Kim, H.-T. Song and B. W. Choi (College of Medicine, Yonsei Univ.), and S. Lee (Center for Neuroscience Imaging Research, IBS) for the MRI measurement and helpful discussion. We also thank B. J. Kong for help on the synthesis of nanoparticles.

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J.-s.C., S.K., D.Y. and J.C. conceived and designed the experiments. J.-s.C., S.K., D.Y. and H.K. performed the experiments and S.H.K. provided EPR analysis data. M.D.G. and A.P. conducted the theoretical calculation. J.-s.C., S.K., D.Y., T.-H.S. and J.C. wrote the paper, and all authors discussed the results and commented on the manuscript.

Corresponding author

Correspondence to Jinwoo Cheon.

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The authors declare no competing financial interests.

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Choi, Js., Kim, S., Yoo, D. et al. Distance-dependent magnetic resonance tuning as a versatile MRI sensing platform for biological targets. Nature Mater 16, 537–542 (2017). https://doi.org/10.1038/nmat4846

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