Nanomedicine: Nanotechnology, Biology and Medicine
Volume 4, Issue 4 , Pages 318-329, December 2008

Nanoimmunoliposome delivery of superparamagnetic iron oxide markedly enhances targeting and uptake in human cancer cells in vitro and in vivo

  • Chengli Yang, PhD

      Affiliations

    • Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC
  • ,
  • Antonina Rait, PhD

      Affiliations

    • Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC
  • ,
  • Kathleen F. Pirollo, PhD

      Affiliations

    • Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC
  • ,
  • John A. Dagata, PhD

      Affiliations

    • National Institute of Standards and Technology, Gaithersburg, MD, USA
  • ,
  • Natalia Farkas, PhD

      Affiliations

    • National Institute of Standards and Technology, Gaithersburg, MD, USA
  • ,
  • Esther H. Chang, PhD

      Affiliations

    • Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC
    • Corresponding Author InformationCorresponding author. Department of Oncology, Lombardi Comprehensive Cancer Center TRB/E420, Georgetown University Medical Center, Washington, DC, USA.

Received 29 September 2007; accepted 20 May 2008. published online 28 July 2008.

Abstract 

To circumvent the problem of reduction of the supermagnetic properties of superparamagnetic iron oxide (SPIO) nanoparticles after chemical modification to conjugate targeting molecules, we have adapted a tumor-targeting nanoimmunoliposome platform technology (scL) to encapsulate and deliver SPIO (scL-SPIO) in vitro and in vivo without chemical modification. Scanning probe microscopy, confocal microscopy, and Prussian blue staining were used to analyze the scL-SPIO and assess intracellular uptake and distribution of SPIO in vitro. In vivo targeting and tumor-specific uptake of scL-SPIO was examined using fluorescent-labeled SPIO. We demonstrated that SPIO encapsulation in the scL complex results in an approximately 11-fold increase in SPIO uptake in human cancer cells in vitro, with distribution to cytoplasm and nucleus. Moreover, the scL nanocomplex specifically and efficiently delivered SPIO into tumor cells after systemic administration, demonstrating the potential of this approach to enhance local tumor concentration and the utility of SPIO for clinical applications.

Key words: Superparamagnetic iron oxide nanoparticles, Nanoimmunoliposome, Tumor targeting, Intracellular uptake, Systemic delivery

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 This work was supported by a National Cancer Institute (NCI) grant 5R01CA132012-02 (E.H.C.) and a research grant from SynerGene Therapeutics, Inc. (SGT) (K.F.P.). These studies were conducted in part using the Microscopy and Imaging, Histopathology and Tissue, and Animal Core Facilities supported by NCI Cancer Center Support grant and US Public Health Service grant 2P30-CA-51008 and 1 S10 RR 15768-01. This investigation was performed in part in a facility constructed with support from Research Facilities Improvement grant C06RR14567 from the National Center for Research Resources, National Institutes of Health. A.R. is a consultant for SGT; E.H.C. is a consultant for SGT, in which she has significant personal financial interest. SGT had no involvement in study design; in the collection, analysis, or interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

PII: S1549-9634(08)00085-3

doi:10.1016/j.nano.2008.05.004

Nanomedicine: Nanotechnology, Biology and Medicine
Volume 4, Issue 4 , Pages 318-329, December 2008