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High-resolution T1 MRI via renally clearable dextran nanoparticles with an iron oxide shell

Nature Biomedical Engineering volume 5, pages 252–263 (2021)Cite this article

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Abstract

Contrast agents for magnetic resonance imaging (MRI) improve anatomical visualizations. However, owing to poor image resolution in whole-body MRI, resolving fine structures is challenging. Here, we report that a nanoparticle with a polysaccharide supramolecular core and a shell of amorphous-like hydrous ferric oxide generating strong T1 MRI contrast (with a relaxivity coefficient ratio of ~1.2) facilitates the imaging, at resolutions of the order of a few hundred micrometres, of cerebral, coronary and peripheral microvessels in rodents and of lower-extremity vessels in rabbits. The nanoparticle can be synthesized at room temperature in aqueous solution and in the absence of surfactants, has blood circulation and renal clearance profiles that prevent opsonization, and leads to better imaging performance than Dotarem (gadoterate meglumine), a clinically approved gadolinium-based MRI contrast agent. The nanoparticle’s biocompatibility and imaging performance may prove advantageous in a broad range of preclinical and clinical applications of MRI.

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Fig. 1: SAIO and its characteristic in vivo behaviours for high-spatial-resolution MRI and renal excretion.
Fig. 2: Characterization of SAIO and its magnetic properties for T1 MRI contrast effects.
Fig. 3: MRI images of a rat head and brain with a spatial resolution of 100 μm.
Fig. 4: SAIO-enhanced MRI images of peripheral regions and whole-body images obtained with SAIO and Dotarem.
Fig. 5: SAIO-enabled MRI visualization of rat coronary vessels.
Fig. 6: SAIO-enhanced MRI images of the lower-extremity vessels of a New Zealand rabbit.
Fig. 7: Pharmacokinetics, excretion and biocompatibility of SAIO.
Fig. 8: Resistance to opsonization and colloidal stability of SAIO.

Data availability

The main data supporting the results of this study are available within the paper and its Supplementary Information. The raw and analysed datasets generated during the study are too large to be shared publicly, but they are available for research purposes from the corresponding authors upon reasonable request.

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Acknowledgements

This work was supported by the Korea Healthcare Technology R&D Project, Ministry for Health & Welfare, Republic of Korea (HI08C2149) and Institute for Basic Science (IBS-R026-D1). We thank H. Y. Kim for helping to synthesize SAIO, K. Kim and B.-K.Yu for helping to perform the TEM analyses, and J. Park for helping to perform the MRI analyses.

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Author notes

  1. These authors contributed equally: Tae-Hyun Shin, Pan Ki Kim.

Authors and Affiliations

  1. Center for Nanomedicine, Institute for Basic Science (IBS), Seoul, Republic of Korea

    Tae-Hyun Shin, Pan Ki Kim, Sunghwi Kang, Jiyong Cheong, Soojin Kim, Yongjun Lim, Wookjin Shin, Joon-Yong Jung, Jungsu D. Lah & Jinwoo Cheon

  2. Department of Chemistry, Yonsei University, Seoul, Republic of Korea

    Tae-Hyun Shin, Sunghwi Kang, Soojin Kim, Yongjun Lim & Jinwoo Cheon

  3. Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea

    Pan Ki Kim & Byoung Wook Choi

  4. Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea

    Pan Ki Kim & Byoung Wook Choi

  5. Graduate Program of Nano Biomedical Engineering (NanoBME), Advanced Science Institute, Yonsei University, Seoul, Republic of Korea

    Jiyong Cheong, Jungsu D. Lah & Jinwoo Cheon

  6. Department of Radiology, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea

    Joon-Yong Jung

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Contributions

T.-H.S., B.W.C. and J. Cheon conceived of and designed the project. T.-H.S., J. Cheong, S. Kang, S. Kim, Y.L., W.S. and J.D.L. synthesized SAIO, performed the material characterizations and conducted the animal experiments. P.K.K., J.-Y.J. and B.W.C. worked on the MRI experiments and analyses. T.-H.S. and J. Cheon wrote the manuscript. All authors discussed the results and commented on the manuscript.

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Correspondence to Byoung Wook Choi or Jinwoo Cheon.

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Competing interests

T.-H.S. is a founder of Inventera Pharmaceuticals, a startup company that develops nanoimaging agents.

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Supplementary Figs. 1–15, Tables 1–4, equation (1) and references.

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Shin, TH., Kim, P.K., Kang, S. et al. High-resolution T1 MRI via renally clearable dextran nanoparticles with an iron oxide shell. Nat Biomed Eng 5, 252–263 (2021). https://doi.org/10.1038/s41551-021-00687-z

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