Journal
JOURNAL OF CONTROLLED RELEASE
Volume 209, Issue -, Pages 159-169Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2015.04.036
Keywords
Cancer metastasis; Circulating tumor cells; Dual antibody conjugates; Capture efficiency; Capture specificity
Funding
- Ministry of Science and Technology of the People's Republic of China [2015CB931804]
- National Natural Science Foundation of China [81273548, 81201709]
- National Institutes of Health [5R01 CA155061]
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Circulating tumor cells (CTCs) have been detected by us and others in cancer patient blood. However, little is known about how to specifically capture and deactivate CTCs in vivo, which may lead to successful metastasis prevention in asymptomatic cancer survivors after surgery. We hypothesize that the dual antibody conjugates may have the advantage of capturing CTCs specifically over their single antibody counterparts. Here we show that the surface-functionalized dendrimers can be sequentially coated with two antibodies directed to surface biomarkers (EpCAM and Slex) of human colorectal CTCs. The dual antibody-coated dendrimers exhibit a significantly enhanced specificity in capturing CTCs in the presence of interfering blood cells, and in both eight-patient bloods and nude mice administered with the labeled CTCs in comparison to their single antibody-coated counterparts. The dual antibody-coated conjugates down-regulate the captured CTCs. This study provides the first conceptual evidence that two antibodies can be biocompatibly conjugated to a nanomaterial to capture and down-regulate CTCs in vivo with the enhanced specificity. (C) 2015 Elsevier B.V. All rights reserved.
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