Artigo De: orcid, cienciavitae

Aptamer-guided acridine derivatives for cervical cancer

Organic & Biomolecular Chemistry

Josué Carvalho; Jéssica Lpes-Nunes; Carla Cruz2019Royal Society of Chemistry

Informações chave

Autores:

Josué Carvalho; Jéssica Lpes-Nunes; Ana Catarina Lopes; Maria Paula Cabral Campello (Maria Paula Cordeiro Crespo Cabral Campello Aboim de Barros); António Paulo (António Manuel Rocha Paulo); João A. Queiróz; Carla Cruz

Publicado em

18/02/2019

Resumo

DNA aptamers represent a way to target cancer cells at a molecular level and continue to be developed with a view to improve treatment and imaging in cancer medicine. AT11-L0, derived from the DNA sequence AT11, forms a single major parallel G-quadruplex (G4) conformation and exhibits an anti-proliferative activity similar to that of AT11 and AS1411 aptamers. On the other side, acridine orange derivatives represent a valuable class of G4 ligands. Herein, we evaluate AT11-L0 G4 as a supramolecular carrier for the delivery of acridine ligands C3, C5 and C8 to HeLa cancer cells. The CD titrations suggest no changes in the chiroptical signal upon addition of an excess of ligands maintaining the parallel G4 topology and C8 stabilizes the structure for more than 20 °C. All the ligands exhibit high affinity (micromolar range) towards AT11-L0 G4, and the respective complexes against nucleolin (nanomolar range) suggesting that the ligands do not negatively affect the recognition of the nucleolin by AT11-L0 G4. NMR studies showed that AT11-L0 forms a G4 containing four G-tetrad layers. Ligand C8 binds AT11-L0 G4 through π–π stacking of the acridine moiety onto the top-tetrad with the involvement of additional interactions with the ligand's side chain and iodobenzene ring. In vitro, the complexes lowered the ligand's cytotoxicity towards non-malignant cells but have a weak inhibitory effect in HeLa cancer cells, except for the AT11-L0-C5 complex. All complexes are efficiently internalized into nucleolin-positive HeLa cells. Overall, these results suggest that AT11-L0 can act as an aptamer by targeting nucleolin and a delivery system of cytotoxic ligands for cervical cancer.

Detalhes da publicação

Autores da comunidade :

Versão da publicação

AO - Versão original do autor

Editora

Royal Society of Chemistry

Ligação para a versão da editora

https://pubs.rsc.org/en/journals/journal/ob

Título do contentor da publicação

Organic & Biomolecular Chemistry

Primeira página ou número de artigo

3002

Volume

17

Fascículo

11

ISSN

1477-0520

WoS (Web of Science)

WOS:000461223700017

Domínio Científico (FOS)

chemical-sciences - Química

Idioma da publicação (código ISO)

eng - Inglês

Identificador alternativo (URI)

http://dx.doi.org/10.1039/c9ob00318e

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Acesso apenas a metadados