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Author Notes:

Hui Mao; Department of radiology and Imaging sciences, Emory University school of Medicine, 1841 Clifton road, Atlanta, GA 30329, USA Tel +1 404 712 0357 Fax +1 404 712 5948 Email: hmao@emory.edu

Lily Yang, Department of Surgery, Emory University School of Medicine, 1364 Clifton Road, Atlanta, GA 30322, USA, Tel +1 404 778 4869, Fax +1 404 778 5112, Email: lyang02@emory.edu

These authors contributed equally to this work

The authors report no conflicts of interest in this work.

Subjects:

Research Funding:

This work is supported in parts by the grant from the National Cancer Institute program project in vivo Cellular and Molecular Imaging Center (P50CA128301-01A10003 to HM and LY), Cancer Nanotechnology Platform Project grant (U01CA151810-02 to HM and LY) and a research grant (R01CA154846-02 to HM and LY) from the National Cancer Institute.

Keywords:

  • magnetic nanoparticles
  • active targeting
  • antifouling
  • breast cancer
  • magnetic resonance imaging

Anti-HER2 antibody and ScFvEGFR-conjugated antifouling magnetic iron oxide nanoparticles for targeting and magnetic resonance imaging of breast cancer

Tools:

Journal Title:

International Journal of Nanomedicine

Volume:

Volume 8

Publisher:

, Pages 3781-3794

Type of Work:

Article | Final Publisher PDF

Abstract:

Antifouling magnetic iron oxide nanoparticles (IONPs) coated with block copolymer poly(ethylene oxide)-block-poly(γ-methacryloxypropyltrimethoxysilane) (PEO-b-PγMPS) were investigated for improving cell targeting by reducing nonspecific uptake. Conjugation of a HER2 antibody, Herceptin®, or a single chain fragment (ScFv) of antibody against epidermal growth factor receptor (ScFvEGFR) to PEO-b-PγMPS-coated IONPs resulted in HER2-targeted or EGFR-targeted IONPs (anti-HER2-IONPs or ScFvEGFR-IONPs). The anti-HER2-IONPs bound specifically to SK-BR-3, a HER2-overexpressing breast cancer cell line, but not to MDA-MB-231, a HER2-underexpressing cell line. On the other hand, the ScFvEGFR-IONPs showed strong reactivity with MDA-MB-231, an EGFR-positive human breast cancer cell line, but not with MDA-MB-453, an EGFR-negative human breast cancer cell line. Transmission electron microscopy revealed internalization of the receptor-targeted nanoparticles by the targeted cancer cells. In addition, both antibody-conjugated and non-antibody-conjugated IONPs showed reduced nonspecific uptake by RAW264.7 mouse macrophages in vitro. The developed IONPs showed a long blood circulation time (serum half-life 11.6 hours) in mice and low accumulation in both the liver and spleen. At 24 hours after systemic administration of ScFvEGFR-IONPs into mice bearing EGFR-positive breast cancer 4T1 mouse mammary tumors, magnetic resonance imaging revealed signal reduction in the tumor as a result of the accumulation of the targeted IONPs.

Copyright information:

© 2013 Chen et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/).

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