Dynamics and Visualization of MCF7 Adenocarcinoma Cell Death by Aptamer-C1q-Mediated Membrane Attack

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dc.contributor.authorStecker, John
dc.contributor.authorSavage, Alissa A.
dc.contributor.authorBruno, John G.
dc.contributor.authorGarcia, Dana M.
dc.contributor.authorKoke, Joseph R.
dc.date.accessioned2016-11-09T19:25:08Z
dc.date.available2016-11-09T19:25:08Z
dc.date.issued2012-11
dc.description.abstractThis study was designed to characterize binding of a DNA aptamer to breast cancer cells and to test whether that aptamer could be used to kill target cells in vitro as part of an aptamer-C1q protein conjugate by coupling to the classic complement cascade. A biotinylated DNA aptamer designated MUC1-5TR-1 was shown to decorate the plasma membranes of human breast adenocarcinoma (MCF7) cells via fluorescence confocal microscopy. Biotinylated aptamer binding successfully initiated the classical complement pathway leading to complement fixation on the target cells via a streptavidin-C1q conjugate as previously reported. Forster Resonance Energy Transfer (FRET) measurements demonstrated membrane depolarization upon aptamer binding, providing indirect evidence of membrane attack complex (MAC) formation as a result of aptamer binding. Transmission electron microscopy (TEM) and immunogold labeling confirmed that aptamer-mediated complement fixation results in MAC formation on the plasma membrane, leading to osmotic swelling and cell death. This approach may provide a much less toxic and more precisely targeted antibody-like treatment for cancers by coupling to the patient's innate immune system in much the same way as more expensive humanized monoclonal antibodies.
dc.description.departmentBiology
dc.formatText
dc.format.extent8 pages
dc.format.medium1 file (.pdf)
dc.identifier.citationStecker, J. R., A. Savage, J. G. Bruno, D. M. García and J. R. Koke. 2012. Dynamics and visualization of MCF7 adenocarcinoma cell death by aptamer-C1q-mediated membrane attack. Nucleic Acid Therapeutics, 22(4), pp. 275-282.
dc.identifier.doihttps://doi.org/10.1089/nat.2012.0355
dc.identifier.urihttps://hdl.handle.net/10877/6355
dc.language.isoen
dc.publisherMary Ann Liebert, Inc.
dc.rights.holder© Mary Ann Liebert, Inc.
dc.sourceNucleic Acid Therapeutics, 2012, Vol. 22, No. 4, pp. 275-282.
dc.subjectbiotinylated DNA aptamer
dc.subjectbreast cancer
dc.subjectaptamer-C1q protein
dc.subjectsreptavidin-C1q conjugate
dc.subjectBiology
dc.titleDynamics and Visualization of MCF7 Adenocarcinoma Cell Death by Aptamer-C1q-Mediated Membrane Attack
dc.typeArticle

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