title: 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.affiliation: Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Hong
authors.forename: Kai
authors.initials: K
authors.lastname: Yang
authors.forename: Yin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Engle
authors.forename: Liangzhu
authors.initials: L
authors.lastname: Feng
authors.forename: Yunan
authors.initials: Y
authors.lastname: Yang
authors.forename: Tapas R
authors.initials: TR
authors.lastname: Nayak
authors.forename: Shreya
authors.initials: S
authors.lastname: Goel
authors.forename: Jero
authors.initials: J
authors.lastname: Bean
authors.forename: Charles P
authors.initials: CP
authors.lastname: Theuer
authors.forename: Todd E
authors.initials: TE
authors.lastname: Barnhart
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Liu
authors.forename: Weibo
authors.initials: W
authors.lastname: Cai
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D045744:Cell Line, Tumor; D003301:Copper Radioisotopes; D000071063:Endoglin; D006108:Graphite / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D007553:Isotope Labeling; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply* / Q000175:diagnosis / Q000378:metabolism / Q000628:therapy; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D058726:Nanoconjugates / Q000737:chemistry*; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging / Q000378:metabolism*; D010087:Oxides / Q000737:chemistry; D049268:Positron-Emission Tomography; D011956:Receptors, Cell Surface / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D003301:Copper Radioisotopes; C064206:ENG protein, human; D000071063:Endoglin; D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; D018796:Immunoconjugates; D058726:Nanoconjugates; D010087:Oxides; D011956:Receptors, Cell Surface; C048993:1,4,7-triazacyclononane-N,N',N''-triacetic acid; D006108:Graphite