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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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.
The authors declare no competing financial interests.
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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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