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Real-time magnetic resonance imaging and quantification of lipoprotein metabolism in vivo using nanocrystals

Nature Nanotechnology volume 4, pages 193–201 (2009)Cite this article

Abstract

Semiconductor quantum dots and superparamagnetic iron oxide nanocrystals have physical properties that are well suited for biomedical imaging. Previously, we have shown that iron oxide nanocrystals embedded within the lipid core of micelles show optimized characteristics for quantitative imaging. Here, we embed quantum dots and superparamagnetic iron oxide nanocrystals in the core of lipoproteins—micelles that transport lipids and other hydrophobic substances in the blood—and show that it is possible to image and quantify the kinetics of lipoprotein metabolism in vivo using fluorescence and dynamic magnetic resonance imaging. The lipoproteins were taken up by liver cells in wild-type mice and displayed defective clearance in knock-out mice lacking a lipoprotein receptor or its ligand, indicating that the nanocrystals did not influence the specificity of the metabolic process. Using this strategy it is possible to study the clearance of lipoproteins in metabolic disorders and to improve the contrast in clinical imaging.

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Figure 1: Schematic of pure and functionalized QD- and SPIO-nanosomes.
Figure 2: Characterization of nanocrystals, QD- and SPIO-nanosomes.
Figure 3: In vitro uptake of QD- and SPIO-nanosomes.
Figure 4: In vivo imaging of intravenously injected QD- and SPIO-nanosomes.
Figure 5: Biodistribution and relaxometry of SPIO-nanosomes in vivo.
Figure 6: Quantitative real-time in vivo imaging of hepatic lipoprotein uptake in wild-type, apolipoprotein E- and LDL-receptor-deficient mice.

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Acknowledgements

The authors thank A. Laatsch, R. Fischer and A. Bartelt for helpful discussions. K. Cornils, B. Holstermann, M. Warmer, S. Ehret and R. Kongi for excellent technical assistance, A. Kornowski for electron microscopy images and R. Capek for providing QD. O.T.B. is supported by a fellowship from the Studienstiftung des Deutschen Volkes. This work was supported by grants from the Deutsche Forschungsgemeinschaft to J.H., U.B. and A.E. (HE3645/2-2, BE829/10-1 and EY16/9-1).

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Authors and Affiliations

  1. IBM II: Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246, Hamburg, Germany

    Oliver T. Bruns, Joachim Lauterwasser, Birgit Mollwitz, Martin Merkel, Ulrike Beisiegel & Joerg Heeren

  2. Department of Diagnostic and Interventional Radiology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246, Hamburg, Germany

    Harald Ittrich, Kersten Peldschus, Michael G. Kaul & Gerhard Adam

  3. Institute of Physical Chemistry, University of Hamburg, Grindelallee 117, D-20146, Hamburg, Germany

    Ulrich I. Tromsdorf, Marija S. Nikolic & Horst Weller

  4. 1. Department of Internal Medicine, Asklepios Clinic St. Georg, Lohmuehlenstrasse 5, D-20099, Hamburg, Germany

    Martin Merkel

  5. Institute of Physical Chemistry and Electrochemistry, TU Dresden, Bergstrasse 66b, D-01062, Dresden, Germany

    Nadja C. Bigall, Sameer Sapra, Rudolph Reimer & Alexander Eychmüller

  6. Department of Electron Microscopy and Micro Technology, Heinrich-Pette Institute, Martinistrasse 52, D-20251, Hamburg, Germany

    Heinz Hohenberg

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Contributions

O.T.B performed and was involved in all aspects of the experiments. O.T.B, U.B. and J.H. designed the study. H.I., K.P., M.G.K. and G.A. performed MRI measurements. U.I.T., N.C.B., M.S.N., S.S., A.E. and H.W. were responsible for synthesis and characterization of nanocrystals. R.R. and H.H. were responsible for electron microscopy. O.T.B, U.I.T., U.B. and J.H. co-wrote the manuscript. All authors discussed the results and commented on the manuscript.

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Correspondence to Oliver T. Bruns.

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Bruns, O., Ittrich, H., Peldschus, K. et al. Real-time magnetic resonance imaging and quantification of lipoprotein metabolism in vivo using nanocrystals. Nature Nanotech 4, 193–201 (2009). https://doi.org/10.1038/nnano.2008.405

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