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

Abstract

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.

Eliminating blood oncogenic exosomes into the small intestine with aptamer-functionalized nanoparticles

“…Artificially intelligent nanomaterials can identify their targets (enzymes, receptors, cells and others) in vivo and selectively bind them 4 . We demonstrated that dual antibodies or dual aptamers conjugated together can capture the rare circulating tumour cells (CTCs) in vivo with high specificity due to their ability to identify two biomarkers on the CTCs and seize them with double hands 5–7 . Drugs can bind circulating human serum albumin, and the binding changes their elimination rate 8 .…”

Aspirin, lysine, mifepristone and doxycycline combined can effectively and safely prevent and treat cancer metastasis: prevent seeds from gemmating on soil

“…The cell cycle was analyzed as we described before [ 57 ]. Briefly, M619 and B16-F10 cells were separately treated with different concentrations of HAMPT (0, 10, 30 and 50 μg/mL) for 24 h. The cells were harvested, washed twice with PBS and fixed in 70% ice-cold ethanol overnight, and then spun to remove ethanol before cellular DNA staining with the fluorescent solution (1% (v/v) Triton X-100, 0.01% RNase, 0.05% PI) for 30 min at 37°C in darkness.…”

Warfarin and coumarin-like Murraya paniculata extract down-regulate EpCAM-mediated cell adhesion: individual components versus mixture for studying botanical metastatic chemopreventives

“…Inspired by the CTC characterization study, we targeted the CTC surface biomarker, in particular the EpCAM, by coating nanomaterial dendrimers with EpCAM antibody to specifically capture blood CTCs and restrain their activity without any cytotoxic effects 6 7 8 . We also demonstrated that a nitric oxide donor compound could inhibit CTCs-initiated metastasis cascade by directly producing vasorelaxation and interfering with hetero-adhesion of cancer cells to vascular endothelium via down-regulating expression of cell adhesion molecules 9 .…”