Article In: orcid, cienciavitae

Aptamer-based Targeted Delivery of a G-quadruplex Ligand in Cervical Cancer Cells

Scientific Reports

Carvalho, Josué; Paiva, Artur; Cruz, Carla — 2019 — Springer

Key information

Authors:

Carvalho, Josué; Paiva, Artur; Cabral Campello, Maria Paula (Maria Paula Cordeiro Crespo Cabral Campello Aboim de Barros); Paulo, António (António Manuel Rocha Paulo); Mergny, Jean-Louis; Salgado, Gilmar F.; Queiroz, João A.; Cruz, Carla

Published in

05/28/2019

Abstract

AS1411 is a G-rich DNA oligonucleotide that functions as an aptamer of the protein nucleolin, found at high levels on the surface of cancer cells but not on the surface of normal cells. Herein, we have studied AS1411 as a supramolecular carrier for the delivery of an acridine-based G-quadruplex ligand, C8, to HeLa cancer cells. Two AS1411 derivatives, LNA-AS1411 and U-AS1411, were also tested, in an attempt to compare AS1411 pharmacological properties. The results showed that AS1411-C8 complexation was made with great binding strength and that it lowered the ligand’s cytotoxicity towards non-malignant cells. This effect was suggested to be due to a decreased internalization of the complexed versus free C8 as shown by flow cytometry. The AS1411 derivatives, despite forming a stable complex with C8, lacked the necessary tumour-selective behaviour. The binding of C8 to AS1411 G-quadruplex structure did not negatively affect the recognition of nucleolin by the aptamer. The AS1411-C8 repressed c-MYC expression at the transcriptional level, possibly due to C8 ability to stabilize the c-MYC promoter G-quadruplexes. Overall, this study demonstrates the usefulness of AS1411 as a supramolecular carrier of the G-quadruplex binder C8 and the potential of using its tumour-selective properties for the delivery of ligands for cancer therapy.

Publication details

Authors in the community:

Publication version

AO - Author's Original

Publisher

Springer

Link to the publisher's version

https://www.nature.com/srep

Title of the publication container

Scientific Reports

First page or article number

7495

Volume

9

Issue

1

ISSN

2045-2322

DOI

10.1038/s41598-019-44388-9

WoS (Web of Science)

WOS:000469217400010

Fields of Science and Technology (FOS)

chemical-sciences - Chemical sciences

Publication language (ISO code)

eng - English

Alternative identifier (URI)

http://dx.doi.org/10.1038/s41598-019-44388-9

Rights type:

Open access

Creative Commons license

CC-BY - CC-BY