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A Synthetic Aptamer-Drug Adduct for Targeted Liver Cancer Therapy

AS1411 (previously known as AGRO100) is a 26 nucleotide guanine-rich DNA aptamer which forms a guanine quadruplex structure. AS1411 has shown promising utility as a treatment for cancers in Phase I and Phase II clinical trials without causing major side-effects. AS1411 inhibits tumor cell growth by...

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Autores principales: Trinh, Thu Le, Zhu, Guizhi, Xiao, Xilin, Puszyk, William, Sefah, Kwame, Wu, Qunfeng, Tan, Weihong, Liu, Chen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4629891/
https://www.ncbi.nlm.nih.gov/pubmed/26523833
http://dx.doi.org/10.1371/journal.pone.0136673
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author Trinh, Thu Le
Zhu, Guizhi
Xiao, Xilin
Puszyk, William
Sefah, Kwame
Wu, Qunfeng
Tan, Weihong
Liu, Chen
author_facet Trinh, Thu Le
Zhu, Guizhi
Xiao, Xilin
Puszyk, William
Sefah, Kwame
Wu, Qunfeng
Tan, Weihong
Liu, Chen
author_sort Trinh, Thu Le
collection PubMed
description AS1411 (previously known as AGRO100) is a 26 nucleotide guanine-rich DNA aptamer which forms a guanine quadruplex structure. AS1411 has shown promising utility as a treatment for cancers in Phase I and Phase II clinical trials without causing major side-effects. AS1411 inhibits tumor cell growth by binding to nucleolin which is aberrantly expressed on the cell membrane of many tumors. In this study, we utilized a simple technique to conjugate a widely-used chemotherapeutic agent, doxorubicin (Dox), to AS1411 to form a synthetic Drug-DNA Adduct (DDA), termed as AS1411-Dox. We demonstrate the utility of AS1411-Dox in the treatment of hepatocellular carcinoma (HCC) by evaluating the targeted delivery of Dox to Huh7 cells in vitro and in a murine xenograft model of HCC.
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spelling pubmed-46298912015-11-13 A Synthetic Aptamer-Drug Adduct for Targeted Liver Cancer Therapy Trinh, Thu Le Zhu, Guizhi Xiao, Xilin Puszyk, William Sefah, Kwame Wu, Qunfeng Tan, Weihong Liu, Chen PLoS One Research Article AS1411 (previously known as AGRO100) is a 26 nucleotide guanine-rich DNA aptamer which forms a guanine quadruplex structure. AS1411 has shown promising utility as a treatment for cancers in Phase I and Phase II clinical trials without causing major side-effects. AS1411 inhibits tumor cell growth by binding to nucleolin which is aberrantly expressed on the cell membrane of many tumors. In this study, we utilized a simple technique to conjugate a widely-used chemotherapeutic agent, doxorubicin (Dox), to AS1411 to form a synthetic Drug-DNA Adduct (DDA), termed as AS1411-Dox. We demonstrate the utility of AS1411-Dox in the treatment of hepatocellular carcinoma (HCC) by evaluating the targeted delivery of Dox to Huh7 cells in vitro and in a murine xenograft model of HCC. Public Library of Science 2015-11-02 /pmc/articles/PMC4629891/ /pubmed/26523833 http://dx.doi.org/10.1371/journal.pone.0136673 Text en © 2015 Trinh et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Trinh, Thu Le
Zhu, Guizhi
Xiao, Xilin
Puszyk, William
Sefah, Kwame
Wu, Qunfeng
Tan, Weihong
Liu, Chen
A Synthetic Aptamer-Drug Adduct for Targeted Liver Cancer Therapy
title A Synthetic Aptamer-Drug Adduct for Targeted Liver Cancer Therapy
title_full A Synthetic Aptamer-Drug Adduct for Targeted Liver Cancer Therapy
title_fullStr A Synthetic Aptamer-Drug Adduct for Targeted Liver Cancer Therapy
title_full_unstemmed A Synthetic Aptamer-Drug Adduct for Targeted Liver Cancer Therapy
title_short A Synthetic Aptamer-Drug Adduct for Targeted Liver Cancer Therapy
title_sort synthetic aptamer-drug adduct for targeted liver cancer therapy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4629891/
https://www.ncbi.nlm.nih.gov/pubmed/26523833
http://dx.doi.org/10.1371/journal.pone.0136673
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