Quick synthesis of a novel combinatorial delivery system of siRNA and doxorubicin for a synergistic anticancer effect

Mengchun Chen,1,2 Ledan Wang,1 Fang Wang,1 Fan Li,3 Weiliang Xia,3 Hongchen Gu,3 Yijie Chen11Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, People’s Republic of China; 2Departme...

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Autores principales:	Chen M, Wang L, Wang F, Li F, Xia W, Gu H, Chen Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	siRNA doxorubicin codelivery system multidrug resistance cancer therapy. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/29905e87c0434ecea2f8dd90caacd0ff
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spelling	oai:doaj.org-article:29905e87c0434ecea2f8dd90caacd0ff2021-12-02T02:34:01ZQuick synthesis of a novel combinatorial delivery system of siRNA and doxorubicin for a synergistic anticancer effect1178-2013https://doaj.org/article/29905e87c0434ecea2f8dd90caacd0ff2019-05-01T00:00:00Zhttps://www.dovepress.com/quick-synthesis-of-a-novel-combinatorial-delivery-system-of-sirna-and--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Mengchun Chen,1,2 Ledan Wang,1 Fang Wang,1 Fan Li,3 Weiliang Xia,3 Hongchen Gu,3 Yijie Chen11Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, People’s Republic of China; 2Department of Pharmacy, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, People’s Republic of China; 3State Key Laboratory of Oncogenes and Related Genes, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200032, People’s Republic of ChinaPurpose: Combining siRNA and other chemotherapeutic agents into one nanocarrier can overcome the multidrug resistance (MDR) phenomenon by synergistically MDR relative genes silencing and elevated chemotherapeutic activity. Most of these systems are typically fabricated through complicated procedures, which involves materials preparation, drug loading and modifications. Herein, the purpose of this study is to develop a new and fast co-delivery system of siRNA and doxorubicin for potentially synergistic cancer treatment.Methods: The co-delivery system is constructed conveniently by a stable complex consisting of doxorubicin bound to siRNA via intercalation firstly, followed by interacting with (3-Aminopropyl)triethoxysilane (APTES) electrostatically and Tetraethyl orthosilicate (TEOS) co-condensed, and the characterizations of the resultant nanocarrier are also investigated. Furthermore, this study evaluates the synergistic anti-cancer efficacy in MCF-7/MDR cells after treatment of siRNA and doxorubicin ‘two in one’ nanocarriers.Results: We establish a new and fast method to craft a co-delivery system of siRNA and doxorubicin with controllable and nearly uniform size, and the entire fabrication process only costs in about 10 minutes. The resultant co-delivery system presents high loading capacities of siRNA and doxorubicin, and the encapsulated doxorubicin plays a pH-responsive control release. Further, biological functionality tests of the synthesized co-delivery nanocarriers show high inhibition of P-gp protein encoded by MDR-1 gene in MCF-7/MDR cells (a variant of human breast cancer cell line with drug resistance) after transfection of these nanocarriers carrying MDR-1 siRNA and doxorubicin simultaneously, which sensitize the MCF-7/MDR cells to doxorubicin, overall leading to improved cell suppression.Conclusion: Collectively, this co-delivery system not only serves as potent therapeutics for synergistic cancer therapy, it also may facilitate the bench-to-bedside translation of combinatorial delivery system as a robust drug nanocarrier by allowing for fabricating a simply and fast nanocarrier for co-delivery of siRNA and doxorubicin with predictable high production rate.Keywords: siRNA, doxorubicin, codelivery system, multidrug resistance, cancer therapyChen MWang LWang FLi FXia WGu HChen YDove Medical PressarticlesiRNAdoxorubicincodelivery systemmultidrug resistancecancer therapy.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 3557-3569 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	siRNA doxorubicin codelivery system multidrug resistance cancer therapy. Medicine (General) R5-920
spellingShingle	siRNA doxorubicin codelivery system multidrug resistance cancer therapy. Medicine (General) R5-920 Chen M Wang L Wang F Li F Xia W Gu H Chen Y Quick synthesis of a novel combinatorial delivery system of siRNA and doxorubicin for a synergistic anticancer effect
description	Mengchun Chen,1,2 Ledan Wang,1 Fang Wang,1 Fan Li,3 Weiliang Xia,3 Hongchen Gu,3 Yijie Chen11Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, People’s Republic of China; 2Department of Pharmacy, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, People’s Republic of China; 3State Key Laboratory of Oncogenes and Related Genes, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200032, People’s Republic of ChinaPurpose: Combining siRNA and other chemotherapeutic agents into one nanocarrier can overcome the multidrug resistance (MDR) phenomenon by synergistically MDR relative genes silencing and elevated chemotherapeutic activity. Most of these systems are typically fabricated through complicated procedures, which involves materials preparation, drug loading and modifications. Herein, the purpose of this study is to develop a new and fast co-delivery system of siRNA and doxorubicin for potentially synergistic cancer treatment.Methods: The co-delivery system is constructed conveniently by a stable complex consisting of doxorubicin bound to siRNA via intercalation firstly, followed by interacting with (3-Aminopropyl)triethoxysilane (APTES) electrostatically and Tetraethyl orthosilicate (TEOS) co-condensed, and the characterizations of the resultant nanocarrier are also investigated. Furthermore, this study evaluates the synergistic anti-cancer efficacy in MCF-7/MDR cells after treatment of siRNA and doxorubicin ‘two in one’ nanocarriers.Results: We establish a new and fast method to craft a co-delivery system of siRNA and doxorubicin with controllable and nearly uniform size, and the entire fabrication process only costs in about 10 minutes. The resultant co-delivery system presents high loading capacities of siRNA and doxorubicin, and the encapsulated doxorubicin plays a pH-responsive control release. Further, biological functionality tests of the synthesized co-delivery nanocarriers show high inhibition of P-gp protein encoded by MDR-1 gene in MCF-7/MDR cells (a variant of human breast cancer cell line with drug resistance) after transfection of these nanocarriers carrying MDR-1 siRNA and doxorubicin simultaneously, which sensitize the MCF-7/MDR cells to doxorubicin, overall leading to improved cell suppression.Conclusion: Collectively, this co-delivery system not only serves as potent therapeutics for synergistic cancer therapy, it also may facilitate the bench-to-bedside translation of combinatorial delivery system as a robust drug nanocarrier by allowing for fabricating a simply and fast nanocarrier for co-delivery of siRNA and doxorubicin with predictable high production rate.Keywords: siRNA, doxorubicin, codelivery system, multidrug resistance, cancer therapy
format	article
author	Chen M Wang L Wang F Li F Xia W Gu H Chen Y
author_facet	Chen M Wang L Wang F Li F Xia W Gu H Chen Y
author_sort	Chen M
title	Quick synthesis of a novel combinatorial delivery system of siRNA and doxorubicin for a synergistic anticancer effect
title_short	Quick synthesis of a novel combinatorial delivery system of siRNA and doxorubicin for a synergistic anticancer effect
title_full	Quick synthesis of a novel combinatorial delivery system of siRNA and doxorubicin for a synergistic anticancer effect
title_fullStr	Quick synthesis of a novel combinatorial delivery system of siRNA and doxorubicin for a synergistic anticancer effect
title_full_unstemmed	Quick synthesis of a novel combinatorial delivery system of siRNA and doxorubicin for a synergistic anticancer effect
title_sort	quick synthesis of a novel combinatorial delivery system of sirna and doxorubicin for a synergistic anticancer effect
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/29905e87c0434ecea2f8dd90caacd0ff
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Quick synthesis of a novel combinatorial delivery system of siRNA and doxorubicin for a synergistic anticancer effect

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