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• W2564783191 endingPage "1428" @default.
• W2564783191 startingPage "1414" @default.
• W2564783191 abstract "AS1411 is a 26-mer G-rich DNA oligonucleotide that forms a variety of G-quadruplex structures. It was identified based on its cancer-selective antiproliferative activity and subsequently determined to be an aptamer to nucleolin, a multifunctional protein that preferentially binds quadruplex nucleic acids and which is present at high levels on the surface of cancer cells. AS1411 has exceptionally efficient cellular internalization compared to non-quadruplex DNA sequences.Recent developments related to AS1411 will be examined, with a focus on its use for targeted delivery of therapeutic and imaging agents.Numerous research groups have used AS1411 as a targeting agent to deliver nanoparticles, oligonucleotides, and small molecules into cancer cells. Studies in animal models have demonstrated that AS1411-linked materials can accumulate selectively in tumors following systemic administration. The mechanism underlying the cancer-targeting ability of AS1411 is not completely understood, but recent studies suggest a model that involves: (1) initial uptake by macropinocytosis, a form of endocytosis prevalent in cancer cells; (2) stimulation of macropinocytosis by a nucleolin-dependent mechanism resulting in further uptake; and (3) disruption of nucleolin-mediated trafficking and efflux leading to cargoes becoming trapped inside cancer cells.Human trials have indicated that AS1411 is safe and can induce durable remissions in a few patients, but new strategies are needed to maximize its clinical impact. A better understanding of the mechanisms by which AS1411 targets and kills cancer cells may hasten the development of promising technologies using AS1411-linked nanoparticles or conjugates for cancer-targeted therapy and imaging. This article is part of a Special Issue entitled G-quadruplex Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio." @default.
• W2564783191 created "2017-01-06" @default.
• W2564783191 creator A5009275052 @default.
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• W2564783191 creator A5068444084 @default.
• W2564783191 creator A5071197441 @default.
• W2564783191 date "2017-05-01" @default.
• W2564783191 modified "2023-10-17" @default.
• W2564783191 title "G-quadruplex oligonucleotide AS1411 as a cancer-targeting agent: Uses and mechanisms" @default.
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