Article In: orcid, cienciavitae
Aptamer-guided acridine derivatives for cervical cancer
Organic & Biomolecular Chemistry
— 2019 — Royal Society of Chemistry
Key information
Authors:
Published in
02/18/2019
Abstract
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.
Publication details
Authors in the community:
António Manuel Rocha Paulo
ist126677
Publication version
AO - Author's Original
Publisher
Royal Society of Chemistry
Link to the publisher's version
https://pubs.rsc.org/en/journals/journal/ob
Title of the publication container
Organic & Biomolecular Chemistry
First page or article number
3002
Volume
17
Issue
11
ISSN
1477-0520
WoS (Web of Science)
Fields of Science and Technology (FOS)
chemical-sciences - Chemical sciences
Publication language (ISO code)
eng - English
Alternative identifier (URI)
http://dx.doi.org/10.1039/c9ob00318e
Rights type:
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