Dissemination　of　circulating　tumor　cells　(CTCs)　in　blood　and　their　hetero-adhesion　to　vascular　endothelial　bed　of　distant　metastatic　secondary　organs　are　the　critical　steps　to　initiate　cancer　metastasis.　The　rarity　of　CTCs　made　their　in　vivo　capture　technically　challenging.　Current　techniques　by　virtue　of　nanostructured　scaffolds　monovalently　conjugated　with　a　single　antibody　and/or　drug　seem　less　efficient　and　specific　in　capturing　CTCs.　Here,　we　report　a　novel　platform　developed　to　re-engineer　nanoscale　dendrimers　for　capturing　CTCs　in　blood　and　interfering　their　adhesion　to　vascular　endothelial　bed　to　form　micrometastatic　foci.　The　nanoscale　dendrimers　were　spatiotemporally　accommodated　with　dual　antibodies　to　target　two　surface　biomarkers　of　colorectal　CTCs.　Physiochemical　characterization,　including　spectra,　fluorescence,　electron　microscope,　dynamic　light　scattering,　electrophoresis,　and　chromatography　analyses,　was　conducted　to　demonstrate　the　successful　conjugation　of　dual　antibodies　to　dendrimer　surface.　The　dual　antibody　conjugates　were　able　to　specifically　recognize　and　bind　CTCs,　moderately　down-regulate　the　activity　of　the　captured　CTCs　by　arresting　them　in　S　phase.　The　related　adhesion　assay　displayed　that　the　dual　antibody　conjugates　interfered　the　hetero-adhesion　of　CTCs　to　fibronectin　(Fn)-coated　substrates　and　human　umbilical　vein　endothelial　cells　(HUVECs).　The　dual　antibody　conjugates　also　showed　the　enhanced　specificity　and　efficiency　in　vitro　and　in　vivo　in　restraining　CTCs　in　comparison　with　their　single　antibody　counterparts.　The　present　study　showed　a　novel　means　to　effectively　prevent　cancer　metastatic　initiation　by　binding,　restraining　CTCs　and　inhibiting　their　hetero-adhesion　to　blood　vessels,　not　by　traditional　cytotoxic-killing　of　cancer　cells.　©　Ivyspring　International　Publisher.