Nanomedicine: Nanotechnology, Biology and Medicine
Volume 4, Issue 3 , Pages 201-207, September 2008

Gadolinium-conjugated TiO2-DNA oligonucleotide nanoconjugates show prolonged intracellular retention period and T1-weighted contrast enhancement in magnetic resonance images

  • Tatjana Paunesku, PhD

      Affiliations

    • Department of Radiation Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
    • Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois, USA
    • Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
    • ,
  • Tianyi Ke, PhD

      Affiliations

    • Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah, USA
    • ,
  • Rohan Dharmakumar, PhD

      Affiliations

    • Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
    • ,
  • Nicole Mascheri, MS

      Affiliations

    • Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
    • ,
  • Aiguo Wu, PhD

      Affiliations

    • Department of Radiation Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
    • ,
  • Barry Lai, PhD

      Affiliations

    • X-ray Science Division, Advanced Photon Source, Argonne National Laboratory, Argonne, Illinois, USA
    • ,
  • Stefan Vogt, PhD

      Affiliations

    • X-ray Science Division, Advanced Photon Source, Argonne National Laboratory, Argonne, Illinois, USA
    • ,
  • Jörg Maser, PhD

      Affiliations

    • X-ray Science Division, Advanced Photon Source, Argonne National Laboratory, Argonne, Illinois, USA
    • ,
  • Kenneth Thurn, BS

      Affiliations

    • Department of Radiation Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
    • ,
  • Barbara Szolc-Kowalska, MD

      Affiliations

    • Department of Radiation Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
    • ,
  • Andrew Larson, PhD

      Affiliations

    • Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
    • ,
  • Raymond C. Bergan, PhD

      Affiliations

    • Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois, USA
    • Department of Medicine, Northwestern University, Chicago, Illinois, USA
    • ,
  • Reed Omary, MD, MS

      Affiliations

    • Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois, USA
    • Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
    • ,
  • Debiao Li, PhD

      Affiliations

    • Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
    • ,
  • Zheng-Rong Lu, PhD

      Affiliations

    • Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah, USA
    • ,
  • Gayle E. Woloschak, PhD

      Affiliations

    • Department of Radiation Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
    • Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois, USA
    • Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
    • Department of Cell and Molecular Biology, Northwestern University, Chicago, Illinois, USA
    • Corresponding Author InformationCorresponding author. Department of Cell and Molecular Biology, Northwestern University, Chicago, IL 60611, USA.

Received 15 September 2007; accepted 13 April 2008. published online 24 June 2008.

Abstract 

Nanoconjugates composed of titanium dioxide (TiO2) nanoparticles, DNA oligonucleotides, and a gadolinium (Gd) contrast agent were synthesized for use in magnetic resonance imaging. Transfection of cultured cancer cells with these nanoconjugates showed them to be superior to the free contrast agent of the same formulation with regard to intracellular accumulation, retention, and subcellular localization. Our results have shown that 48 hours after treatment, the concentration of Gd in nanoconjugate-treated cells was 1000-fold higher than in cells treated with contrast agent alone. Consequently, T1-weighted contrast enhancements were observed in cells treated with nanoconjugates but not in cells treated by the contrast agent alone. This type of nanoconjugate with increased retention time, Gd accumulation, and intracellular delivery may find its use in Gd neutron-capture cancer therapy.

Key words: Nanoconjugates, Magnetic resonance imaging, Subcellular targeting

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 This work was supported in part by the following National Institutes of Health grants: CA107467, EB002100, P50 CA89018, U54CA119341; by Department of Energy (DOE) grant FG02-04 ER 63920; and by Siemens Medical Solutions. Use of the Advanced Photon Source was supported by the US DOE, Office of Science, Office of Basic Energy Sciences, under Contract No. W-31-109-Eng-38.

PII: S1549-9634(08)00046-4

doi:10.1016/j.nano.2008.04.004

Nanomedicine: Nanotechnology, Biology and Medicine
Volume 4, Issue 3 , Pages 201-207, September 2008

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