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Geometrical confinement of gadolinium-based contrast agents in nanoporous particles enhances T1 contrast

Abstract

Magnetic resonance imaging contrast agents are currently designed by modifying their structural and physiochemical properties to improve relaxivity and to enhance image contrast. Here, we show a general method for increasing relaxivity by confining contrast agents inside the nanoporous structure of silicon particles. Magnevist, gadofullerenes and gadonanotubes were loaded inside the pores of quasi-hemispherical and discoidal particles. For all combinations of nanoconstructs, a boost in longitudinal proton relaxivity r1 was observed: Magnevist, r1 ≈ 14 mM−1 s−1/Gd3+ ion (8.15 × 10+7 mM−1 s−1/construct); gadofullerenes, r1 ≈ 200 mM−1 s−1/Gd3+ ion (7 × 10+9 mM−1 s−1/construct); gadonanotubes, r1 ≈ 150 mM−1 s−1/Gd3+ ion (2 × 10+9 mM−1 s−1/construct). These relaxivity values are about 4 to 50 times larger than those of clinically available gadolinium-based agents (4 mM−1 s−1/Gd3+ ion). The enhancement in contrast is attributed to the geometrical confinement of the agents, which influences the paramagnetic behaviour of the Gd3+ ions. Thus, nanoscale confinement offers a new and general strategy for enhancing the contrast of gadolinium-based contrast agents.

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Figure 1: The new MRI nanoconstructs.
Figure 2: Concentration of Gd3+ ions in the SiMP nanoconstruct as determined by ICP-OES analysis.
Figure 3: MRI characterization of the nanoconstruct by a benchtop relaxometer.
Figure 4: MRI characterization of the H-SiMP/GNT nanoconstruct in a clinical scanner.
Figure 5: Calculated longitudinal relaxivity for the SiMP/MAG and SiMP/GF nanoconstructs.
Figure 6: NMRD profiles for the GNT and SiMP/GNT constructs.

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Acknowledgements

This work was supported by Telemedicine and Advanced Technology Research Center (TATRC)-United States Army Medical Research Acquisition Activity (USAMRAA) through the pre-centre grant W81XWH-09-2-0139 of the Alliance for Nano Health. This work was also partially supported through grants from the Department of Defense (USA) (DOD)W81XWH-09-1-0212 and the National Institutes of Health (USA) (NIH) U54CA143837 at UTHSC-H, by the Robert A. Welch Foundation (grant C-0627), the NIH U54CA143837 grant, and the Nanoscale Science and Engineering Initiative under the NSF EEC-0647452 at Rice University, by the Swiss National Science Foundation and EU COST Action D38 ‘Metal Based Systems for Molecular Imaging Applications’ at École Polytechnique Fédérale de Lausanne (EPFL), and through NIH grant R43CA128277-02 at TDA. The authors would like to thank L. A. Tran for assistance with SEM imaging, J. Conyers for allowing the use of the benchtop relaxometer and M. Landry for all the graphical work.

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J.S.A. designed the experimental plan, performed all the experiments and helped in writing the manuscript. B.G. designed the experimental plan, developed the protocols for loading, and helped in the loading experiments and in writing the manuscript. R.S. helped in performing the loading experiments and the ICP analysis. L.M. performed MRI characterization. X.L coordinated the microfabrication of the SiMPs and performed their surface modification. R.E.S. performed the SEM analysis. R.K. and R.M. performed the MRI characterization in clinical scanners. R.D.B. manufactured the GFs. L.H. helped in performing the MRI characterization of the GNT, provided input on the original draft and revisions. M.F. provided input on the original draft and revisions. L.J.W. conceived the idea, designed the experimental plan and helped in writing the manuscript. P.D. conceived the idea, designed the experimental plan, wrote the manuscript and performed all the numerical calculations. All the authors discussed the results and commented on the manuscript.

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Correspondence to Paolo Decuzzi.

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Ananta, J., Godin, B., Sethi, R. et al. Geometrical confinement of gadolinium-based contrast agents in nanoporous particles enhances T1 contrast. Nature Nanotech 5, 815–821 (2010). https://doi.org/10.1038/nnano.2010.203

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