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Multifunctional Mesoporous Silica Nanospheres with Cleavable Gd(III) Chelates as MRI Contrast Agents: Synthesis, Characterization, Target-Specificity, and Renal Clearance†

  1. Juan L. Vivero-Escoto1,
  2. Kathryn M. L. Taylor-Pashow2,
  3. Rachel C. Huxford1,
  4. Joseph Della Rocca1,
  5. Christie Okoruwa1,
  6. Hongyu An3,
  7. Weili Lin3,
  8. Wenbin Lin1,*

Article first published online: 9 NOV 2011

DOI: 10.1002/smll.201100521

Issue

Small

Small

Volume 7, Issue 24, pages 3519–3528, December 16, 2011

Additional Information

How to Cite

Vivero-Escoto, J. L., Taylor-Pashow, K. M. L., Huxford, R. C., Della Rocca, J., Okoruwa, C., An, H., Lin, W. and Lin, W. (2011), Multifunctional Mesoporous Silica Nanospheres with Cleavable Gd(III) Chelates as MRI Contrast Agents: Synthesis, Characterization, Target-Specificity, and Renal Clearance. Small, 7: 3519–3528. doi: 10.1002/smll.201100521

Author Information

  1. 1

    Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina, 27599, USA

  2. 2

    Savannah River National Laboratory, Aiken, South Carolina 29808, USA

  3. 3

    Department of Radiology, University of North Carolina, Chapel Hill, North Carolina, 27599, USA

*Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina, 27599, USA.

  1. †

    Dedicated to Prof. Chad A. Mirkin to celebrate 20 years of his extraordinary contributions to science.

Publication History

  1. Issue published online: 12 DEC 2011
  2. Article first published online: 9 NOV 2011
  3. Manuscript Revised: 31 MAY 2011
  4. Manuscript Received: 17 MAR 2011

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Keywords:

  • contrast agents;
  • silica nanospheres;
  • biodegradable;
  • magnetic resonance imaging;
  • target-specific nanoparticles

Graphical Abstract

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Multifunctional mesoporous silica nanospheres (MSNs) with cleavable Gd(III) chelates are synthesized and evaluated as magnetic resonance imaging contrast agents. The MSNs are grafted with Gd(III) chelates via a redox-responsive disulfide moiety. These MSNs are then further functionalized with polyethylene glycol and anisamide to impart biocompatibility and target specificity. The Gd(III) chelate is quickly cleaved by the blood pool thiols and eliminated via renal excretion.

Abstract

Mesoporous silica nanospheres (MSNs) are a promising material for magnetic resonance imaging (MRI) contrast agents. In this paper multifunctional MSNs with cleavable Gd(III) chelates are synthesized and characterized, and their applicability as MRI contrast agents is demonstrated both in vitro and in vivo. The MSNs contain Gd(III) chelates that are covalently linked via a redox-responsive disulfide moiety. The MSNs are further functionalized with polyethylene glycol (PEG) and an anisamide ligand to improve their biocompatibility and target specificity. The effectiveness of MSNs as an MRI imaging contrast agent and their targeting ability are successfully demonstrated in vitro using human colon adenocarcinoma and pancreatic cancer cells. Finally, the capability of this platform as an in vivo MRI contrast agent is tested using a 3T scanner. The Gd(III) chelate was quickly cleaved by the blood pool thiols and eliminated through the renal excretion pathway. Further tuning of the Gd(III) chelate release kinetics is needed before the MSN system can be used as target-specific MRI contrast agents in vivo.

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