Theranostics 2014; 4(12):1250-1263. doi:10.7150/thno.8775
The Architecture and Biological Function of Dual Antibody-Coated Dendrimers: Enhanced Control of Circulating Tumor cells and Their Hetero-Adhesion to Endothelial Cells for Metastasis Prevention
1. Cancer Metastasis Alert and Prevention Center, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
2. Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ, 08854, USA.
3. Department of Medicine Oncology, East Hospital of Xiamen University, Fuzhou 350004, China.
4. Biopharmaceutical photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou 350002, China.
Xie J, Zhao R, Gu S, Dong H, Wang J, Lu Y, Sinko PJ, Yu T, Xie F, Wang L, Shao J, Jia L. The Architecture and Biological Function of Dual Antibody-Coated Dendrimers: Enhanced Control of Circulating Tumor cells and Their Hetero-Adhesion to Endothelial Cells for Metastasis Prevention. Theranostics 2014; 4(12):1250-1263. doi:10.7150/thno.8775. Available from http://www.thno.org/v04p1250.htm
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.
Keywords: Cancer metastasis, Circulating tumor cells, PAMAM dendrimers, Dual antibody conjugation, Cell binding and regulation, Cell adhesion.