Anti-nucleolin aptamer AS1411: an advancing therapeutic

Abstract

Targeted therapy is highly desirable, as it allows for selective cytotoxicity on diseased cells without off-target side effects. Nucleolin is a remarkable target for cancer therapy given its high abundance, selective presence on the plasma membrane, and multifaceted influence on the initiation and progression of cancer. Nucleolin is a protein overexpressed on the cell membrane in many tumors and serves as a binding protein for several ligands implicated in angiogenesis and tumorigenesis. Nucleolin is present in the cytoplasm, nucleoplasm, and nucleolus and is used by selected pathogens for cell entry. AS1411 is a guanosine-rich oligonucleotide aptamer that binds nucleolin and is internalized in the tumor cells. AS1411 is well tolerated at therapeutic doses and localizes to tumor cells overexpressing nucleolin. AS1411 has a good safety profile with efficacy in relapsed acute myeloid leukemia and renal cell carcinoma producing mild or moderate side effects. The promising potential of AS1411 is its ability to be conjugated to drugs and nanoparticles. When a drug is bound to AS1411, the drug will localize to tumor cells leading to targeted therapy with fewer systemic side effects than traditional practices. AS1411 can also be bound to nanoparticles capable of detecting nucleolin at concentrations far lower than lab techniques used today for cancer diagnosis. AS1411 has a promising potential to change cancer diagnoses and treatment.

Multifunctional molecular hybrid for targeted colorectal cancer cells: Integrating doxorubicin, AS1411 aptamer, and T9/U4 ASO

“…Notably, the cell viability of SW480 cells treated with AS-T9/U4_MH was lower compared to those treated with nonAS-T9/U4_MH. This specificity can be attributed to the presence of AS1411 aptamer within the molecular hybrid, as the aptamer is capable of recognizing nucleolin molecules present on the surface membrane of SW480 cells [49]. Research by Emilio et al further supports the specificity of AS1411 aptamer, demonstrating its ability to significantly inhibit the phosphorylation of nucleolin in human umbilical vein endothelial cells (HUVEC), whereas control formulations such as scramble sequences and ranibizumab had no effect on nucleolin phosphorylation [50].…”

Myogenic Anti-Nucleolin Aptamer iSN04 Inhibits Proliferation and Promotes Differentiation of Vascular Smooth Muscle Cells

“…Our results of nucleolin antagonism by iSN04 are consistent with these findings and provide a novel biomolecule for nucleolin inhibition in VSMCs. It is known that overexpression and/or abnormal subcellular localization of nucleolin is also involved in tumor growth [ 31 ] and viral infection [ 32 ]. The 26-base guanine-rich anti-nucleolin aptamer, AS1411, has been used in phase II clinical trials for acute myeloid leukemia and renal cell carcinoma [ 33 ], which confirmed the safety and anti-proliferative effect of nucleolin inhibition by aptamers.…”

Role of Exosomes in Cancer and Aptamer-Modified Exosomes as a Promising Platform for Cancer Targeted Therapy

“…AS1411 is a well-known 26-base guanine-rich oligodeoxyribonucleotide aptamer that forms a G-quadruplex structure with many advantageous characteristics to bind specifically to nucleolin [ 401 ]. Nucleolin is a multifunctional protein localizing in the nucleolus, nucleoplasm, cytoplasm and cell membrane, which has been found to be overexpressed in a variety of cancers [ 402 ]. Thus, a large number of AS1411-based strategies have been developed in cancer targeted therapy so far [ 403 ].…”