Journal
CHEMBIOCHEM
Volume 15, Issue 9, Pages 1268-1273Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.201402100
Keywords
cancer; CD20; DNA nanotechnology; multivalency; rolling circle amplification
Funding
- Department of Pharmaceutical Sciences at the Sue and Bill Gross Stem Cell Research Center
- Chao Family Comprehensive Cancer Center at University of California Irvine
- National Natural Science Foundation of China [51103179]
- Natural Science Foundation of Shandong Province, China [ZR2011BL017]
- Fundamental Research Funds for the Central Universities
- China Scholarship Council [CSC 201206455009]
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We report a simple, versatile, multivalent ligand system that is capable of specifically and efficiently modulating cell-surface receptor clustering and function. The multivalent ligand is made of a polymeric DNA scaffold decorated with biorecognition ligands (i.e., antibodies) to interrogate and modulate cell receptor signaling and function. Using CD20 clustering-mediated apoptosis in B-cell cancer cells as a model system, we demonstrated that our multivalent ligand is significantly more effective at inducing apoptosis of target cancer cells than its monovalent counterpart. This multivalent DNA material approach represents a new chemical biology tool to interrogate cell receptor signaling and functions and to potentially manipulate such functions for the development of therapeutics.
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