2. Academic Validation
  3. G-quadruplex oligonucleotide AS1411 as a cancer-targeting agent: Uses and mechanisms

G-quadruplex oligonucleotide AS1411 as a cancer-targeting agent: Uses and mechanisms

  • Biochim Biophys Acta Gen Subj. 2017 May;1861(5 Pt B):1414-1428. doi: 10.1016/j.bbagen.2016.12.015.
Paula J Bates 1,  Elsa M Reyes-Reyes 2,  Mohammad T Malik 3,  Emily M Murphy 4,  Martin G O'Toole 4,  John O Trent 3
Affiliations

Affiliations

  • 1 Department of Medicine, University of Louisville, USA; James Graham Brown Cancer Center, University of Louisville, USA. Electronic address: [email protected].
  • 2 Department of Medicine, University of Arizona, USA.
  • 3 Department of Medicine, University of Louisville, USA; James Graham Brown Cancer Center, University of Louisville, USA.
  • 4 Department of Biomedical Engineering, University of Louisville, USA.
PMID: 28007579 DOI: 10.1016/j.bbagen.2016.12.015
Abstract

Background: 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.

Scope of review: Recent developments related to AS1411 will be examined, with a focus on its use for targeted delivery of therapeutic and imaging agents.

Major conclusions: 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.

Significance: 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.

Keywords

AS1411; Aptamer; Cancer; Contrast agent; Drug delivery; Imaging; Nanoparticles; Nucleolin; Quadruplex; Radiosensitizer.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-147081
    Oligonucleotide Aptamer