Nucleolin was originally described as a nuclear and cytoplasmic protein; however, a number of recent studies have shown that it can also be expressed at the cell surface.59,60 Nucleolin is involved in the organization of the nuclear chromatin, rDNA transcription, packaging of the pre-RNA, ribosome assembly, nucleocytoplasmic transport, cytokinesis, nucleogenesis, and apoptosis. AS-1411 (formerly AGRO100) is an aptamer capable of making G-quadruplexes that bind to nucleolin on the cell surface61 and interact with the nuclear factor kappa B (NFkB) essential modulator (NEMO) inside the cell.62 The cytosolic localization of AS-1411 after binding to cell surface nucleolin may be exploited for the intracellular delivery of nanoparticles to cancer cells. The use of AS-1411 as a therapeutic modality has also shown promise for the treatment of cancer in humans, and Antisoma of United Kingdom is evaluating this aptamer in phase-I clinical trials.63 The therapeutic benefit of AS-1411 is presumably attributed to the disruption of the NFkB signaling inside the cells.64

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