In vivo targeting and imaging of tumor vasculature with radiolabeled, antibody-conjugated nanographene.

Abstract

Herein we demonstrate that nanographene can be specifically directed to the tumor neovasculature in vivo through targeting of CD105 (i.e., endoglin), a vascular marker for tumor angiogenesis. The covalently functionalized nanographene oxide (GO) exhibited excellent stability and target specificity. Pharmacokinetics and tumor targeting efficacy of the GO conjugates were investigated with serial noninvasive positron emission tomography imaging and biodistribution studies, which were validated by in vitro, in vivo, and ex vivo experiments. The incorporation of an active targeting ligand (TRC105, a monoclonal antibody that binds to CD105) led to significantly improved tumor uptake of functionalized GO, which was specific for the neovasculature with little extravasation, warranting future investigation of these GO conjugates for cancer-targeted drug delivery and/or photothermal therapy to enhance therapeutic efficacy. Since poor extravasation is a major hurdle for nanomaterial-based tumor targeting in vivo, this study also establishes CD105 as a promising vascular target for future cancer nanomedicine.

• Authors: Hao Hong, Kai Yang, Yin Zhang, Jonathan W Engle, Liangzhu Feng, Yunan Yang, Tapas R Nayak, Shreya Goel, Jero Bean, Charles P Theuer, Todd E Barnhart, Zhuang Liu, Weibo Cai
• Journal: ACS nano (ACS Nano) Vol. 6 Issue 3 Pg. 2361-70 (Mar 27 2012) ISSN: 1936-086X [Electronic] United States
• PMID: 22339280 (Publication 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.)
• Copyright: © 2012 American Chemical Society

Chemical References

• Antibodies, Monoclonal
• Antigens, CD
• Copper Radioisotopes
• ENG protein, human
• Endoglin
• Heterocyclic Compounds
• Heterocyclic Compounds, 1-Ring
• Immunoconjugates
• Nanoconjugates
• Oxides
• Receptors, Cell Surface
• 1,4,7-triazacyclononane-N,N',N''-triacetic acid
• Graphite

Topics

• Animals
• Antibodies, Monoclonal (chemistry, immunology)
• Antigens, CD (immunology)
• Cell Line, Tumor
• Copper Radioisotopes
• Endoglin
• Graphite (chemistry)
• Heterocyclic Compounds (chemistry)
• Heterocyclic Compounds, 1-Ring
• Human Umbilical Vein Endothelial Cells (metabolism)
• Humans
• Immunoconjugates (chemistry, metabolism, pharmacokinetics)
• Isotope Labeling
• Mammary Neoplasms, Experimental (blood supply, diagnosis, metabolism, therapy)
• Mice
• Molecular Imaging (methods)
• Nanoconjugates (chemistry)
• Neovascularization, Pathologic (diagnostic imaging, metabolism)
• Oxides (chemistry)
• Positron-Emission Tomography
• Receptors, Cell Surface (immunology)