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.
At a glance
- Snapshot magnetic resonance imaging. Angew. Chem. Int. Ed. 43, 5456–5464 (2004).
- Gadolinium(III) chelates as MRI contrast agents: structure, dynamics and applications. Chem. Rev. 99, 2293–2352 (1999). , , &
- Paramagnetic metal complexes as water proton relaxation agents for NMR imaging: theory and design. Chem. Rev. 87, 901–927 (1987).
- 2001). & The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging (John Wiley & Sons,
- A market summary report for MRI is available at http://www.imvinfo.com/
- Comparative study of the physicochemical properties of six clinical low molecular weight gadolinium contrast agents. Contrast Media Mol. Imaging 1, 128–137 (2006). , &
- Relaxivity of gadolinium(III) complexes: theory and mechanism, in The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging 45–119 (John Wiley & Sons, 2001). , &
- Mesoporous silicon particles as a multistage delivery system for imaging and therapeutic applications. Nature Nanotech. 3, 151–157 (2008). et al.
- Water-soluble gadofullerenes: toward high-relaxivity, pH-responsive MRI contrast agents. J. Am. Chem. Soc. 127, 799–805 (2005). et al.
- The differential cytotoxicity of water-soluble fullerenes. Nano Lett. 4, 1881–1887 (2004). et al.
- Superparamagnetic gadonanotubes are high-performance MRI contrast agents. Chem. Commun. 31, 3915–3917 (2005). et al.
- Gadonanotubes as ultrasensitive pH-smart probes for magnetic resonance imaging. Nano Lett. 8, 415–419 (2008). et al.
- Functionalization of individual ultra-short single-walled carbon nanotubes. Nanotechnology 17, 5033–5037 (2006). et al.
- Tailored porous silicon microparticles: fabrication and properties. Chem. Phys. Chem. 11, 1029–1035 (2010). et al.
- Fluid enhancement of particle transport in nanochannels. Phys. Fluids 18, 117102–117108 (2006). &
- Nanoparticulate assemblies of amphiphiles and diagnostically active materials for multimodality imaging. Acc. Chem. Res. 42, 904–914 (2009). et al.
- Relaxivity of liposomal paramagnetic MRI contrast agents. Magn. Reson. Mater. Phys., Biol. Med. 18, 186–192 (2005). et al.
- Dendrimer-based nanoprobe for dual modality magnetic resonance and fluorescence imaging. Nano Lett. 6, 1459–1463 (2006). et al.
- Maximizing the relaxivity of HSA-bound gadolinium complexes by simultaneous optimization of rotation and water exchange. Chem. Commun. 45, 4726–4728 (2007). et al.
- Rational design of protein-based MRI contrast agents. J. Am. Chem. Soc. 130, 9260–9267 (2008). et al.
- Noncovalent functionalization of carbon nanotubes with amphiphilic Gd3+ chelates: toward powerful T1 and T2 MRI contrast agents. Nano Lett. 8, 232–236 (2008). et al.
- Understanding paramagnetic relaxation phenomena for water-soluble gadofullerenes. J. Phys. Chem. C 111, 5633–5639 (2007). et al.
- Destroying gadofullerene aggregates by salt addition in aqueous solution of Gd@C60(OH)x and Gd@C60[C(COOH2)]. J. Am. Chem. Soc. 127, 9368–9369 (2005). et al.
- General treatment of paramagnetic relaxation enhancement associated with translational diffusion. J. Chem. Phys. 130, 174104–174112 (2009). &
- Second coordination sphere water molecules and relaxivity of gadolinium(III) complexes: implications for MRI contrast agents. Eur. J. Inorg. Chem. 2000, 399–407 (2000).
- Phosphinic derivative of DTPA conjugated to a G5 PAMAM dendrimer: an 17O and 1H relaxation study of its Gd(III) complex. Dalton Trans. 28, 3399–3406 (2006). et al.
- The adhesive strength of non-spherical particles mediated by specific interactions. Biomaterials 27, 5307–5314 (2006). &
- Intravascular delivery of particulate systems: does geometry really matter? Pharm. Res. 26, 235–243 (2009). , , &
- Size and shape effects in the biodistribution of intravascularly injected particles. J. Control. Release 141, 320–327 (2009). et al.
- Multistage mesoporous silicon-based nanocarriers: biocompatibility and controlled degradation in physiological fluids. CRS Newsletter 25, 9–11 (2008). et al.
- Can receptors be imaged with MRI agents? Q. J. Nucl. Med. 41, 155–162 (1997). , &
- Sustained small interfering RNA delivery by mesoporous silicon particles. Cancer Res. 70, 3687–3696 (2010). et al.
- Porous silicon in drug delivery devices and materials. Adv. Drug Deliv. Rev. 60, 1266–1277 (2008). , , &
- Biodegradable luminescent porous silicon nanoparticles for in vivo applications. Nature Mater. 8, 331–336 (2009). et al.
- Mesoporous silica nanoparticles as controlled release drug delivery and gene transfection carriers. Adv. Drug Deliv., Rev. 60, 1278–1288 (2008). , , &
- Cutting single-wall carbon nanotubes through fluorination. Nano Lett. 2, 1009–1013 (2002). , , , &
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