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

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

10610 - Biophysics

Projekt

<a href="/cs/project/EF15_003%2F0000477" target="_blank" >EF15_003/0000477: Strukturní gymnastika nukleových kyselin: od molekulárních principů přes biologické funkce k terapeutickým cílům.</a><br>

Návaznosti

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

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

Scientific Reports

ISSN

2045-2322

e-ISSN

—

Svazek periodika

9

Číslo periodika v rámci svazku

MAY 28 2019

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

12

Strana od-do

7945

Kód UT WoS článku

000469217400010

EID výsledku v databázi Scopus

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