Future Perspectives of Therapeutic, Diagnostic and Prognostic Aptamers in Eye Pathological Angiogenesis

Iturriaga-Goyón, Emilio; Buentello-Volante, Beatríz; Magaña‐Guerrero, Fátima Sofía; Garfias, Yonathan

doi:10.3390/cells10061455

Cited by 6 publications

(7 citation statements)

References 202 publications

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“…The chemical production presents lower costs compared to therapeutic antibodies, and they are not immunogenic. All these properties make them suitable for biomedical applications [ 46 , 79 ]. AS1411 is an aptamer that specifically binds to NCL, it has anti-proliferative effects over tumor cells, inhibits NF-κB pro-survival mechanism, blocks DNA-replication and induces cell cycle arrest.…”

Section: Discussionmentioning

confidence: 99%

“…Aptamers are short single-stranded oligonucleotides that have biological properties that overcome monoclonal antibodies. They have unlimited targets, short production time, cost-effective, thermally stable, high level of tissue penetration and are non-immunogenic (reviewed in [ 46 ]). In the present work we describe cell surface NCL as a specific target to reduce pathological angiogenesis by means of using nucleolin-binding aptamers AS1411.…”

Section: Introductionmentioning

confidence: 99%

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AS1411 Nucleolin-Specific Binding Aptamers Reduce Pathological Angiogenesis through Inhibition of Nucleolin Phosphorylation

Iturriaga-Goyón

Vivanco-Rojas

Magaña‐Guerrero

et al. 2021

IJMS

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Proliferative retinopathies produces an irreversible type of blindness affecting working age and pediatric population of industrialized countries. Despite the good results of anti-VEGF therapy, intraocular and systemic complications are often associated after its intravitreal use, hence novel therapeutic approaches are needed. The aim of the present study is to test the effect of the AS1411, an antiangiogenic nucleolin-binding aptamer, using in vivo, ex vivo and in vitro models of angiogenesis and propose a mechanistic insight. Our results showed that AS1411 significantly inhibited retinal neovascularization in the oxygen induced retinopathy (OIR) in vivo model, as well as inhibited branch formation in the rat aortic ex vivo assay, and, significantly reduced proliferation, cell migration and tube formation in the HUVEC in vitro model. Importantly, phosphorylated NCL protein was significantly abolished in HUVEC in the presence of AS1411 without affecting NFκB phosphorylation and -21 and 221-angiomiRs, suggesting that the antiangiogenic properties of this molecule are partially mediated by a down regulation in NCL phosphorylation. In sum, this new research further supports the NCL role in the molecular etiology of pathological angiogenesis and identifies AS1411 as a novel anti-angiogenic treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

AS1411 Nucleolin-Specific Binding Aptamers Reduce Pathological Angiogenesis through Inhibition of Nucleolin Phosphorylation

Iturriaga-Goyón

Vivanco-Rojas

Magaña‐Guerrero

et al. 2021

IJMS

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“…162,163 However, clinical applications of lncRNAs and aptamers are still in their infancy. 38,161 MCT inhibitors that interfere with lactate transmembrane transport have been studied for their application as glycolysis inhibitors, including a phase I clinical trial of AZD3965, a potent selective and orally available MCT1 inhibitor. 164 The inhibitor promoted intracellular lactate accumulation that counteracted its use for biosynthetic synthesis resulting in reduced tumor growth.…”

Section: Inhibitors Of Glycolysis For Therapeutic Application In Ocul...mentioning

confidence: 99%

New Insights in ATP Synthesis as Therapeutic Target in Cancer and Angiogenic Ocular Diseases

van Noorden,

Yetkin-Arik,

Serrano Martinez

et al. 2024

J Histochem Cytochem.

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Lactate and ATP formation by aerobic glycolysis, the Warburg effect, is considered a hallmark of cancer. During angiogenesis in non-cancerous tissue, proliferating stalk endothelial cells (ECs) also produce lactate and ATP by aerobic glycolysis. In fact, all proliferating cells, both non-cancer and cancer cells, need lactate for the biosynthesis of building blocks for cell growth and tissue expansion. Moreover, both non-proliferating cancer stem cells in tumors and leader tip ECs during angiogenesis rely on glycolysis for pyruvate production, which is used for ATP synthesis in mitochondria through oxidative phosphorylation (OXPHOS). Therefore, aerobic glycolysis is not a specific hallmark of cancer but rather a hallmark of proliferating cells and limits its utility in cancer therapy. However, local treatment of angiogenic eye conditions with inhibitors of glycolysis may be a safe therapeutic option that warrants experimental investigation. Most types of cells in the eye such as photoreceptors and pericytes use OXPHOS for ATP production, whereas proliferating angiogenic stalk ECs rely on glycolysis for lactate and ATP production. (J Histochem Cytochem XX.XXX–XXX, XXXX)

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“…However, the therapeutic use of these antibodies presents some drawbacks such as their high cost, short half-life, the occurrence of side effects (e.g., inflammation, retinal detachment, or increased ocular pressure), or the need for repeated intravitreal injections to administrate the antibodies. Furthermore, some patients do not respond favorably to anti-VEGF, and it is recommended to switch the treatment to corticosteroids such as dexamethasone [ 17 ]. As an alternative to antibodies, aptamers have emerged as a promising approach to inhibit the angiogenic process of the retina [ 18 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Assessment of Aptamer as a Potential Drug Targeted Delivery for Retinal Angiogenesis Inhibition

et al. 2023

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AT11-L0 is an aptamer derivative of AS1411 composed of G-rich sequences that can adopt a G-quadruplex (G4) structure and target nucleolin (NCL), a protein that acts as a co-receptor for several growth factors. Hence, this study aimed to characterize the AT11-L0 G4 structure and its interaction with several ligands for NCL targeting and to evaluate their capacity to inhibit angiogenesis using an in vitro model. The AT11-L0 aptamer was then used to functionalize drug-associated liposomes to increase the bioavailability of the aptamer-based drug in the formulation. Biophysical studies, such as nuclear magnetic resonance, circular dichroism, and fluorescence titrations, were performed to characterize the liposomes functionalized with the AT11-L0 aptamer. Finally, these liposome formulations with the encapsulated drugs were tested on the human umbilical vein endothelial cell (HUVEC) model to assess their antiangiogenic capacity. The results showed that the AT11-L0 aptamer–ligand complexes are highly stable, presenting melting temperatures from 45 °C to 60 °C, allowing for efficient targeting of NCL with a KD in the order of nM. The aptamer-functionalized liposomes loaded with ligands C8 and dexamethasone did not show cytotoxic effects in HUVEC cells compared with the free ligands and AT11-L0, as assessed by cell viability assays. AT11-L0 aptamer-functionalized liposomes encapsulating C8 and dexamethasone did not present a significant reduction in the angiogenic process when compared with the free ligands. In addition, AT11-L0 did not show anti-angiogenic effects at the concentrations tested. However, C8 shows potential as an angiogenesis inhibitor, which should be further developed and optimized in future experiments.

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Future Perspectives of Therapeutic, Diagnostic and Prognostic Aptamers in Eye Pathological Angiogenesis

Cited by 6 publications

References 202 publications

AS1411 Nucleolin-Specific Binding Aptamers Reduce Pathological Angiogenesis through Inhibition of Nucleolin Phosphorylation

AS1411 Nucleolin-Specific Binding Aptamers Reduce Pathological Angiogenesis through Inhibition of Nucleolin Phosphorylation

New Insights in ATP Synthesis as Therapeutic Target in Cancer and Angiogenic Ocular Diseases

Assessment of Aptamer as a Potential Drug Targeted Delivery for Retinal Angiogenesis Inhibition

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