ArticleCancer research2010
A new paradigm for aptamer therapeutic AS1411 action: uptake by macropinocytosis and its stimulation by a nucleolin-dependent mechanism.
Article in Cancer research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 197 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
197 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Nucleolin‑based targeting strategies in cancer treatment: Focus on cancer immunotherapy (Review).International journal of molecular medicine · 2023Pooled it
- Proximity Proteomics Maps Candidate Cellular Uptake Pathways for Cell-Derived Nanovesicles.Small methods · 2026Article
- Review
- Multi-Technique Integration Identifies O-GlcNAc Transferase in Fibroblast-Like Synoviocytes as a Therapeutic Target for Rheumatoid Arthritis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- An Integrated DNA Nanoprobe for Intranuclear Imaging and In Situ Profiling of OGG1 Activity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Proteomic Characterization of AS1411 Reveals ATP6AP1 as a Mediator of Triple-Negative Breast Cancer Progression.Proteomics · 2026Article
- Development of AS1411 Aptamer-Targeted Solid Lipid Nanoparticles to Improve Anticancer Efficiency of Lawsone.Advanced pharmaceutical bulletin · 2026Article
- Extracellular Vesicle-Mediated Nucleolin Transfer in Glioblastoma: A Targetable Axis Driving Blood-Tumour Barrier Formation.Journal of extracellular vesicles · 2026Article
- Discovery of synthetic G-quadruplex DNA as SARS-CoV-2 helicase inhibitor with antiviral, anti-inflammatory and antioxidative properties.Cell death discovery · 2026Article
- Development of AS1411 aptamer-conjugated chitosan-carbon dot nanocarriers for targeted drug delivery and fluorescent imaging in breast cancer therapy.Journal of biological engineering · 2026Article
- Review
- Aptamer-liposome targeted nanotherapeutics for cancer therapy: Bibliometric analysis, recent developments and future perspectives.Materials today. Bio · 2026Review
- Modulating a Massive Set of Biomolecular Structures by Sono-Mechanical Force.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- AS1411-functionalized albumin nanoparticles for nucleolin-targeted realgar delivery and therapy in triple-negative breast cancer.Frontiers in pharmacology · 2026Article
- A Theoretical Framework for Ligand-Functionalised Magnetic Lipid Nanoparticles in Glioblastoma Therapy.Cancers · 2025Review
- Nucleolin perturbation alters membrane lipid homeostasis.Molecular omics · 2025Article
- Universal Microfluidic Platform for Multifunctional Surface Modification of Small Extracellular Vesicles.Journal of extracellular vesicles · 2025Article
- Enhancing the intracellular delivery of antisense oligonucleotides (ASO) : a comparative study of aptamer, vitamin E, and cholesterol ASO conjugates.RSC advances · 2025Article
- Disruption of the Nucleolin-CXCR4 interaction by the DNA aptamer HY-4 halts colorectal cancer metastasis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
137 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
AS1411 is a first-in-class anticancer agent, currently in phase II clinical trials. It is a quadruplex-forming oligodeoxynucleotide that binds to nucleolin as an aptamer, but its mechanism of action is not completely understood. Mechanistic insights could lead to clinically useful markers for AS1411 response and to novel targeted therapies. Previously, we proposed a model where cell surface nucleolin serves as the receptor for AS1411, leading to selective uptake in cancer cells. Here, we compare uptake of fluorophore-labeled AS1411 (FL-AS1411) in DU145 prostate cancer cells (sensitive to AS1411) and Hs27 nonmalignant skin fibroblasts (resistant to AS1411). Uptake of FL-AS1411 occurred by endocytosis in both cell types and was much more efficient than an inactive, nonquadruplex oligonucleotide. Unexpectedly, uptake of FL-AS1411 was lower in cancer cells compared with Hs27 cells. However, the mechanism of uptake was different, occurring by macropinocytosis in cancer cells, but by a nonmacropinocytic pathway in Hs27 cells. Additionally, treatment of various cancer cells with AS1411 caused hyperstimulation of macropinocytosis, provoking an increase in its own uptake, whereas no stimulation was observed for nonmalignant cells. Nucleolin was not required for initial FL-AS1411 uptake in DU145 cells but was necessary for induced macropinocytosis and FL-AS1411 uptake at later times. Our results are inconsistent with the previous mechanistic model but confirm that nucleolin plays a role in mediating AS1411 effects. The data suggest a new model for AS1411 action as well as a new role for nucleolin in stimulating macropinocytosis, a process with potential applications in drug delivery.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.