Therapeutic applications of AS1411 aptamer, an update review

Yazdian‐Robati, Rezvan; Bayat, Payam; Oroojalian, Fatemeh; Zargari, Mehryar; Ramezani, Mohammad; Taghdisi, Seyed Mohammad; Abnous, Khalil

doi:10.1016/j.ijbiomac.2019.11.118

Cited by 185 publications

(105 citation statements)

References 116 publications

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“…Despite mounting evidence that NCL is a valid therapeutic target in different types of aggressive cancer [ 29 , 32 , 57 , 59 , 60 ], the data for PCa are lacking. In the present study we aimed to demonstrate that targeting surface NCL by the scFv 4LB5 is an effective way to inhibit multiple neoplastic features of PCa cells.…”

Section: Discussionmentioning

confidence: 99%

NCL Inhibition Exerts Antineoplastic Effects against Prostate Cancer Cells by Modulating Oncogenic MicroRNAs

Sheetz

Mills

Tessari

et al. 2020

Cancers

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Prostate cancer (PCa) is the most frequently diagnosed cancer in men and second most common cause of cancer-related deaths in the United States. Androgen deprivation therapy (ADT) is only temporarily effective for advanced-stage PCa, as the disease inevitably progresses to castration-resistant prostate cancer (CRPC). The protein nucleolin (NCL) is overexpressed in several types of human tumors where it is also mislocalized to the cell surface. We previously reported the identification of a single-chain fragment variable (scFv) immuno-agent that is able to bind NCL on the surface of breast cancer cells and inhibit proliferation both in vitro and in vivo. In the present study, we evaluated whether NCL could be a valid therapeutic target for PCa, utilizing DU145, PC3 (CRPC), and LNCaP (androgen-sensitive) cell lines. First, we interrogated the publicly available databases and noted that higher NCL mRNA levels are associated with higher Gleason Scores as well as with recurrent and metastatic tumors. Then, using our anti-NCL scFv, we demonstrated that NCL is expressed on the surface of all three tested cell lines and that NCL inhibition results in reduced proliferation and migration. We also measured the inhibitory effect of NCL targeting on the biogenesis of oncogenic microRNAs such as miR-21, -221 and -222, which was cell context dependent. Taken together, our data provide evidence that NCL targeting inhibits the key hallmarks of malignancy in PCa cells and may provide a novel therapeutic option for patients with advanced-stage PCa.

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Section: Discussionmentioning

confidence: 99%

NCL Inhibition Exerts Antineoplastic Effects against Prostate Cancer Cells by Modulating Oncogenic MicroRNAs

Sheetz

Mills

Tessari

et al. 2020

Cancers

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“…According to a recent review [ 26 ], nucleolin is one of the most abundant non-ribosomal phosphoproteins of nucleoli. However, in several cancers, nucleolin is highly expressed both intracellularly and on the cell surface, which led to the development of the aptamer AS1411, a 26-base guanine (G)-rich quadruplex oligodeoxynucleotide [ 27 ] ( Fig.…”

Section: Targeted Deliverymentioning

confidence: 99%

Recent advances in aptamer applications for analytical biochemistry

Zon

2022

Analytical Biochemistry

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Aptamers are typically defined as relatively short (20–60 nucleotides) single-stranded DNA or RNA molecules that bind with high affinity and specificity to various types of targets. Aptamers are frequently referred to as “synthetic antibodies” but are easier to obtain, less expensive to produce, and in several ways more versatile than antibodies. The beginnings of aptamers date back to 1990, and since then there has been a continual increase in aptamer publications. The intent of the present account was to focus on recent original research publications, i.e., those appearing in 2019 through April 2020, when this account was written. A Google Scholar search of this recent literature was performed for relevance-ranking of articles. New methods for selection of aptamers were not included. Nine categories of applications were organized and representative examples of each are given. Finally, an outlook is offered focusing on “faster, better, cheaper” application performance factors as key drivers for future innovations in aptamer applications.

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“…The original AS1411 aptamer mentioned above is a 26-nucleotide guanosine-rich DNA-aptamer with high affinity and specificity to nucleolin, a cell-surface receptor overexpressed in cancer cells. Because AS1411 has not only proven anti-cancer effects in models of various cancer entities, but is also an enhancer of cellular uptake, it is frequently used for the generation of aptamerbased drug delivery systems [57]. According to expectations, it was reported that an increased loading density of AS1411 on gold nanostars (AuNS) rises the quantity of AS1411 delivered into pancreatic cancer cells, which finally results in substantial pancreatic cancer cell death [61].…”

Section: Aptamers For the Detection Of Circulating Cancer Cells (Ctcsmentioning

confidence: 99%

Aptamers: a novel targeted theranostic platform for pancreatic ductal adenocarcinoma

Maier

et al. 2020

Radiat Oncol

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Pancreatic ductal adenocarcinoma (PDAC) is an extremely challenging disease with a high mortality rate and a short overall survival time. The poor prognosis can be explained by aggressive tumor growth, late diagnosis, and therapy resistance. Consistent efforts have been made focusing on early tumor detection and novel drug development. Various strategies aim at increasing target specificity or local enrichment of chemotherapeutics as well as imaging agents in tumor tissue. Aptamers have the potential to provide early detection and permit anti-cancer therapy with significantly reduced side effects. These molecules are in-vitro selected single-stranded oligonucleotides that form stable threedimensional structures. They are capable of binding to a variety of molecular targets with high affinity and specificity. Several properties such as high binding affinity, the in vitro chemical process of selection, a variety of chemical modifications of molecular platforms for diverse function, non-immunoreactivity, modification of bioavailability, and manipulation of pharmacokinetics make aptamers attractive targets compared to conventional cell-specific ligands. To explore the potential of aptamers for early diagnosis and targeted therapy of PDAC-as single agents and in combination with radiotherapy-we summarize the generation process of aptamers and their application as biosensors, biomarker detection tools, targeted imaging tracers, and drug-delivery carriers. We are furthermore discussing the current implementation aptamers in clinical trials, their limitations and possible future utilization.

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Therapeutic applications of AS1411 aptamer, an update review

Cited by 185 publications

References 116 publications

NCL Inhibition Exerts Antineoplastic Effects against Prostate Cancer Cells by Modulating Oncogenic MicroRNAs

NCL Inhibition Exerts Antineoplastic Effects against Prostate Cancer Cells by Modulating Oncogenic MicroRNAs

Recent advances in aptamer applications for analytical biochemistry

Aptamers: a novel targeted theranostic platform for pancreatic ductal adenocarcinoma

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