期刊
ACS NANO
卷 6, 期 3, 页码 2361-2370出版社
AMER CHEMICAL SOC
DOI: 10.1021/nn204625e
关键词
nanographene; tumor angiogenesis; positron emission tomography (PET); CD105 (endoglin); molecular imaging; Cu-64; cancer
类别
资金
- University of Wisconsin Carbone Cancer Center
- Department of Defense [W81XWH-11-1-0644, W81XWH-11-1-0648]
- NCRR [1UL1RR025011]
- National Basic Research Program (973 Program) of China [2012CB932600, 2011CB911002]
- National Natural Science Foundation of China [51132006, 51002100]
- NIH through the UW [5 T32 CA009206-32]
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 (THC105, 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.
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