Artigo De: cienciavitae

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

Pharmaceuticals

David Moreira; Jéssica Lopes-Nunes; Carla Cruz2023MDPI AG

Informações chave

Autores:

David Moreira; Jéssica Lopes-Nunes; Fátima Milhano Santos; Maria Paula Cabral Campello (Maria Paula Cordeiro Crespo Cabral Campello Aboim de Barros); cristina oliveira; António Paulo; C. T. Tomaz; Carla Cruz

Publicado em

16/05/2023

Resumo

<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>

Detalhes da publicação

Autores da comunidade :

Versão da publicação

VoR - Versão publicada

Editora

MDPI AG

Título do contentor da publicação

Pharmaceuticals

Primeira página ou número de artigo

751

Volume

16

Fascículo

5

ISSN

1424-8247

Domínio Científico (FOS)

chemical-sciences - Química

Idioma da publicação (código ISO)

eng - Inglês

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