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Inhibition of cell proliferation through an ATP-responsive co-delivery system of doxorubicin and Bcl-2 siRNA

Herein, DNA duplex was constructed through the hybridization of adenosine triphosphate (ATP)-responsive aptamer and its cDNA in which GC-rich motif could be used to load doxorubicin (DOX), and then, cationic polymer PEI25K was used as a carrier to simultaneously condense DOX-Duplex and Bcl-2 siRNA t...

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Autores principales: Zhang, Jianxu, Wang, Yudi, Chen, Jiawen, Liang, Xiao, Han, Haobo, Yang, Yan, Li, Quanshun, Wang, Yanbo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503501/
https://www.ncbi.nlm.nih.gov/pubmed/28740380
http://dx.doi.org/10.2147/IJN.S135086
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author Zhang, Jianxu
Wang, Yudi
Chen, Jiawen
Liang, Xiao
Han, Haobo
Yang, Yan
Li, Quanshun
Wang, Yanbo
author_facet Zhang, Jianxu
Wang, Yudi
Chen, Jiawen
Liang, Xiao
Han, Haobo
Yang, Yan
Li, Quanshun
Wang, Yanbo
author_sort Zhang, Jianxu
collection PubMed
description Herein, DNA duplex was constructed through the hybridization of adenosine triphosphate (ATP)-responsive aptamer and its cDNA in which GC-rich motif could be used to load doxorubicin (DOX), and then, cationic polymer PEI25K was used as a carrier to simultaneously condense DOX-Duplex and Bcl-2 siRNA to prepare the ternary nanocomplex polyethylenimine (PEI)/DOX-Duplex/siRNA. The ATP concentration gradient between the cytosol and extracellular environment could achieve the stable loading of DOX in duplex and the rapid drug release in an ATP-responsive manner. Using human prostate tumor cell line PC-3 as a model, an obvious induction of cell proliferation could be detected with a cell viability of 53.3%, which was stronger than single cargo delivery, indicating the synergistic effect between these two components. The enhanced anti-proliferative effect of ternary nanocomplex could be attributed to the improved induction of cell apoptosis in a mitochondria-mediated pathway and cell-cycle arrest at the G2 phase. Overall, the ATP-responsive nanocarrier for co-delivering DOX and Bcl-2 siRNA has been demonstrated to be a smart delivery system with favorable anti-proliferative effect, especially for solving the multidrug resistance of tumors.
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spelling pubmed-55035012017-07-24 Inhibition of cell proliferation through an ATP-responsive co-delivery system of doxorubicin and Bcl-2 siRNA Zhang, Jianxu Wang, Yudi Chen, Jiawen Liang, Xiao Han, Haobo Yang, Yan Li, Quanshun Wang, Yanbo Int J Nanomedicine Original Research Herein, DNA duplex was constructed through the hybridization of adenosine triphosphate (ATP)-responsive aptamer and its cDNA in which GC-rich motif could be used to load doxorubicin (DOX), and then, cationic polymer PEI25K was used as a carrier to simultaneously condense DOX-Duplex and Bcl-2 siRNA to prepare the ternary nanocomplex polyethylenimine (PEI)/DOX-Duplex/siRNA. The ATP concentration gradient between the cytosol and extracellular environment could achieve the stable loading of DOX in duplex and the rapid drug release in an ATP-responsive manner. Using human prostate tumor cell line PC-3 as a model, an obvious induction of cell proliferation could be detected with a cell viability of 53.3%, which was stronger than single cargo delivery, indicating the synergistic effect between these two components. The enhanced anti-proliferative effect of ternary nanocomplex could be attributed to the improved induction of cell apoptosis in a mitochondria-mediated pathway and cell-cycle arrest at the G2 phase. Overall, the ATP-responsive nanocarrier for co-delivering DOX and Bcl-2 siRNA has been demonstrated to be a smart delivery system with favorable anti-proliferative effect, especially for solving the multidrug resistance of tumors. Dove Medical Press 2017-07-03 /pmc/articles/PMC5503501/ /pubmed/28740380 http://dx.doi.org/10.2147/IJN.S135086 Text en © 2017 Zhang et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Zhang, Jianxu
Wang, Yudi
Chen, Jiawen
Liang, Xiao
Han, Haobo
Yang, Yan
Li, Quanshun
Wang, Yanbo
Inhibition of cell proliferation through an ATP-responsive co-delivery system of doxorubicin and Bcl-2 siRNA
title Inhibition of cell proliferation through an ATP-responsive co-delivery system of doxorubicin and Bcl-2 siRNA
title_full Inhibition of cell proliferation through an ATP-responsive co-delivery system of doxorubicin and Bcl-2 siRNA
title_fullStr Inhibition of cell proliferation through an ATP-responsive co-delivery system of doxorubicin and Bcl-2 siRNA
title_full_unstemmed Inhibition of cell proliferation through an ATP-responsive co-delivery system of doxorubicin and Bcl-2 siRNA
title_short Inhibition of cell proliferation through an ATP-responsive co-delivery system of doxorubicin and Bcl-2 siRNA
title_sort inhibition of cell proliferation through an atp-responsive co-delivery system of doxorubicin and bcl-2 sirna
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503501/
https://www.ncbi.nlm.nih.gov/pubmed/28740380
http://dx.doi.org/10.2147/IJN.S135086
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