Article In: cienciavitae
Assessment of Aptamer as a Potential Drug Targeted Delivery for Retinal Angiogenesis Inhibition
Pharmaceuticals
— 2023 — MDPI AG
Key information
Authors:
Published in
05/16/2023
Abstract
<jats:p>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.</jats:p>
Publication details
Authors in the community:
Publication version
VoR - Version of Record
Publisher
MDPI AG
Title of the publication container
Pharmaceuticals
First page or article number
751
Volume
16
Issue
5
ISSN
1424-8247
Fields of Science and Technology (FOS)
chemical-sciences - Chemical sciences
Publication language (ISO code)
eng - English
Alternative identifier (URI)
https://scholar.tecnico.ulisboa.pt/records/aqSP2As4EUDtHH5P39sIpa2c4rrxlhHaD9yV
Rights type:
Only metadata available