| Glypican-3 targeting of liver cancer cells using multifunctional nanoparticles. | |
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MedLine Citation:
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PMID: 21303616 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Imaging is essential in accurately detecting, staging, and treating primary liver cancer (hepatocellular carcinoma [HCC]), one of the most prevalent and lethal malignancies. We developed a novel multifunctional nanoparticle (NP) specifically targeting glypican-3 (GPC3), a proteoglycan implicated in promotion of cell growth that is overexpressed in most HCCs. Quantitative real-time polymerase chain reaction was performed to confirm the differential GPC3 expression in two human HCC cells, Hep G2 (high) and HLF (negligible). These cells were treated with biotin-conjugated GPC3 monoclonal antibody (αGPC3) and subsequently targeted using superparamagnetic iron oxide NPs conjugated to streptavidin and Alexa Fluor 647. Flow cytometry demonstrated that only GPC3-expressing Hep G2 cells were specifically targeted using this αGPC3-NP conjugate (fourfold mean fluorescence over nontargeted NP), and magnetic resonance imaging (MRI) experiments showed similar findings (threefold R2 relaxivity). Confocal fluorescence microscopy localized the αGPC3 NPs only to the cell surface of GPC3-expressing Hep G2 cells. Further characterization of this construct demonstrated a negatively charged, monodisperse, 50 nm NP, ideally suited for tumor targeting. This GPC3-specific NP system, with dual-modality imaging capability, may enhance pretreatment MRI, enable refined intraoperative HCC visualization by near-infrared fluorescence, and be potentially used as a carrier for delivery of tumor-targeted therapies, improving patient outcomes. |
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Authors:
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James O Park; Zachary Stephen; Conroy Sun; Omid Veiseh; Forrest M Kievit; Chen Fang; Matthew Leung; Hyejung Mok; Miqin Zhang |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Molecular imaging Volume: 10 ISSN: 1536-0121 ISO Abbreviation: Mol Imaging Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-02-09 Completed Date: 2011-05-26 Revised Date: 2012-02-02 |
Medline Journal Info:
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Nlm Unique ID: 101120118 Medline TA: Mol Imaging Country: United States |
Other Details:
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Languages: eng Pagination: 69-77 Citation Subset: IM |
Affiliation:
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Departments of Surgery, Materials Science and Engineering, and Radiology, University of Washington, Seattle, WA 98195-2120, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antibodies, Monoclonal
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chemistry,
immunology Cell Line, Tumor Cyclic AMP / analogs & derivatives, chemistry Flow Cytometry Glypicans / immunology, metabolism* Hep G2 Cells Humans Liver Neoplasms / diagnosis*, metabolism* Magnetic Resonance Imaging Nanoparticles / chemistry* Nanotechnology Streptavidin / chemistry |
| Grant Support | |
ID/Acronym/Agency:
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R01 CA119408-04/CA/NCI NIH HHS; R01 CA119408-04S1/CA/NCI NIH HHS; R01 CA134213-03/CA/NCI NIH HHS; R01 EB006043-04/EB/NIBIB NIH HHS; R01CA119408/CA/NCI NIH HHS; R01CA134213/CA/NCI NIH HHS; R01EB006043/EB/NIBIB NIH HHS; T32 CA138312-01/CA/NCI NIH HHS; T32CA138312/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 0/Glypicans; 39824-30-1/8-aminohexylamino cAMP; 60-92-4/Cyclic AMP; 9013-20-1/Streptavidin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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