Enhanced Specificity in Capturing and Restraining Circulating Tumor Cells with Dual Antibody–Dendrimer Conjugates

Specifically capturing and restraining residual circulating tumor cells (CTCs) in cancer patients are the sine qua non for safely and effectively preventing cancer metastasis, to which the current chemotherapy has been limited due to its toxicity. Moreover, because of CTCs’ rarity and low activity, the current technology for capturing CTCs based solely on a single surface biomarker has limited capacity and is used mainly for in vitro diagnosis. Here, it is possible to sequentially conjugate two CTCs antibodies (aEpCAM and aSlex) to the functionalized dendrimers to specifically capture human hepatocellular CTCs in both artificial and clinical patient blood samples, and restrain their activities. The molecular entities of the conjugates are demonstrated by various means. The dual antibody conjugate captured CTCs threefold more than the single counterparts from the high concentrations of interfering red blood cells or leukocytes, as well as from the blood of liver cancer patients, and exhibits the superiority to their single counterparts in down-regulating the captured CTCs. These results collectively provide the strong evidence that two antibodies can be compatibly conjugated to a nanomaterial, resulting in an enhanced specificity in restraining CTCs in blood.