title: DNA-scaffolded multivalent ligands to modulate cell function.
abstract: 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.
authors.affiliation: State Key Laboratory of Heavy Oil Processing, College of Science, China University of Petroleum, 66 Changjiang (West) Rd, Huangdao, Qingdao, 266580 (P. R. China); Department of Pharmaceutical Sciences, Department of Biomedical Engineering, Sue and Bill Gross Stem Cell Research Center and Chao Family Comprehensive Cancer Center, and Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California, Irvine, 845 Health Sciences Road, Irvine, CA 92697 (USA) http://faculty.sites.uci.edu/zhaolab/
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Zhang
authors.forename: Mark A
authors.initials: MA
authors.lastname: Eckert
authors.forename: M Monsur
authors.initials: MM
authors.lastname: Ali
authors.forename: Linan
authors.initials: L
authors.lastname: Liu
authors.forename: Dong-Ku
authors.initials: DK
authors.lastname: Kang
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Chang
authors.forename: Egest J
authors.initials: EJ
authors.lastname: Pone
authors.forename: Leonard S
authors.initials: LS
authors.lastname: Sender
authors.forename: David A
authors.initials: DA
authors.lastname: Fruman
authors.forename: Weian
authors.initials: W
authors.lastname: Zhao
mesh_terms: D000906:Antibodies / Q000378:metabolism*; D017209:Apoptosis; D004247:DNA / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D008024:Ligands; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D000906:Antibodies; D008024:Ligands; D011956:Receptors, Cell Surface; D004247:DNA
keywords: CD20; DNA nanotechnology; cancer; multivalency; rolling circle amplification