Ex vivo and in vivo capture and deactivation of circulating tumor cells by dual-antibody-coated nanomaterials

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.