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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F19%3A00509884" target="_blank" >RIV/68081707:_____/19:00509884 - isvavai.cz</a>

Result on the web

<a href="https://www.nature.com/articles/s41598-019-44388-9.pdf" target="_blank" >https://www.nature.com/articles/s41598-019-44388-9.pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41598-019-44388-9" target="_blank" >10.1038/s41598-019-44388-9</a>

Result language

angličtina

Original language name

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

Original language description

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, C-8, 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-C-8 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 C-8 as shown by flow cytometry. The AS1411 derivatives, despite forming a stable complex with C-8, lacked the necessary tumour-selective behaviour. The binding of C-8 to AS1411 G-quadruplex structure did not negatively affect the recognition of nucleolin by the aptamer. The AS1411-C-8 repressed c-MYC expression at the transcriptional level, possibly due to C-8 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 C-8 and the potential of using its tumour-selective properties for the delivery of ligands for cancer therapy.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10610 - Biophysics

Project

<a href="/en/project/EF15_003%2F0000477" target="_blank" >EF15_003/0000477: Structural gymnastics of nucleic acids: from molecular principles through biological functions to therapeutic targets.</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Scientific Reports

ISSN

2045-2322

e-ISSN

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Volume of the periodical

9

Issue of the periodical within the volume

MAY 28 2019

Country of publishing house

GB - UNITED KINGDOM

Number of pages

12

Pages from-to

7945

UT code for WoS article

000469217400010

EID of the result in the Scopus database

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