Codelivery of temozolomide and siRNA with polymeric nanocarrier for effective glioma treatment

Yuan Peng,1,2 Jinsheng Huang,2 Hong Xiao,2 Teng Wu,1 Xintao Shuai1,2 1Center of Biomedical Engineering, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China; 2Key Laboratory for Polymeric Composite & Functional Materials of Ministry of Education, Department of Polym...

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Autores principales:	Peng Y, Huang J, Xiao H, Wu T, Shuai X
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	polymeric nanocarrier temozolomide siRNA targeting BCL-2 gene glioma treatment drug resistance. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/03db54d7b5124995b41695c65c87b5d1
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spelling	oai:doaj.org-article:03db54d7b5124995b41695c65c87b5d12021-12-02T00:27:05ZCodelivery of temozolomide and siRNA with polymeric nanocarrier for effective glioma treatment1178-2013https://doaj.org/article/03db54d7b5124995b41695c65c87b5d12018-06-01T00:00:00Zhttps://www.dovepress.com/codelivery-of-temozolomide-and-sirna-with-polymeric-nanocarrier-for-ef-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yuan Peng,1,2 Jinsheng Huang,2 Hong Xiao,2 Teng Wu,1 Xintao Shuai1,2 1Center of Biomedical Engineering, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China; 2Key Laboratory for Polymeric Composite & Functional Materials of Ministry of Education, Department of Polymer Science, School of Materials Science and Engineering, Sun Yat-Sen University, Guangzhou 510275, China Background: The treatment of glioma remains a challenge because conventional chemotherapy is often ineffective by drug resistance. Combinative therapy using chemotherapeutic agents and siRNA has demonstrated potential to improve anticancer outcome through a synergistic effect in various cancers. The current study aims to achieve better glioma treatment through a combinative therapy based on a folate-targeted nanocarrier carrying both temozolomide (TMZ) and anti-BCL-2 siRNA.Methods: A polymeric micelle (TMZ-FaPEC@siRNA) incorporating TMZ and anti-BCL-2 siRNA was prepared based on folate-conjugated triblock copolymer (Fa-PEG-PEI-PCL, Fa-PEC) of poly(ε-caprolactone) (PCL), poly(ethylenimine) (PEI) and poly(ethylene glycol) (PEG). The physicochemical properties and drug release profile of TMZ-FaPEC@siRNA were tested. The Fa-targeted drug delivery and joint effect of siRNA and TMZ to induce glioma apoptosis and tumor growth inhibition were evaluated both in vitro and in vivo.Results: In vitro cell study demonstrated that the nanocarrier effectively facilitates codelivery of siRNA and TMZ into C6 cells, resulting in a strong apoptotic response of cancer cells by silencing the antiapoptosis BCL-2 gene and activating the proapoptotic Bax gene simultaneously. In vivo study in rat bearing orthotropic glioma showed that tumor growth was inhibited and meanwhile animal survival was prolonged remarkably through intracranial injection of TMZ-FaPEC@siRNA.Conclusion: Our results evidence the strong efficacy of the folate-targeted nanomedicine carrying TMZ and BCL-2 siRNA in treating glioma. Keywords: polymeric nanocarrier, temozolomide, siRNA targeting BCL-2 gene, glioma treatment, drug resistancePeng YHuang JXiao HWu TShuai XDove Medical Pressarticlepolymeric nanocarriertemozolomidesiRNA targeting BCL-2 geneglioma treatmentdrug resistance.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 3467-3480 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	polymeric nanocarrier temozolomide siRNA targeting BCL-2 gene glioma treatment drug resistance. Medicine (General) R5-920
spellingShingle	polymeric nanocarrier temozolomide siRNA targeting BCL-2 gene glioma treatment drug resistance. Medicine (General) R5-920 Peng Y Huang J Xiao H Wu T Shuai X Codelivery of temozolomide and siRNA with polymeric nanocarrier for effective glioma treatment
description	Yuan Peng,1,2 Jinsheng Huang,2 Hong Xiao,2 Teng Wu,1 Xintao Shuai1,2 1Center of Biomedical Engineering, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China; 2Key Laboratory for Polymeric Composite & Functional Materials of Ministry of Education, Department of Polymer Science, School of Materials Science and Engineering, Sun Yat-Sen University, Guangzhou 510275, China Background: The treatment of glioma remains a challenge because conventional chemotherapy is often ineffective by drug resistance. Combinative therapy using chemotherapeutic agents and siRNA has demonstrated potential to improve anticancer outcome through a synergistic effect in various cancers. The current study aims to achieve better glioma treatment through a combinative therapy based on a folate-targeted nanocarrier carrying both temozolomide (TMZ) and anti-BCL-2 siRNA.Methods: A polymeric micelle (TMZ-FaPEC@siRNA) incorporating TMZ and anti-BCL-2 siRNA was prepared based on folate-conjugated triblock copolymer (Fa-PEG-PEI-PCL, Fa-PEC) of poly(ε-caprolactone) (PCL), poly(ethylenimine) (PEI) and poly(ethylene glycol) (PEG). The physicochemical properties and drug release profile of TMZ-FaPEC@siRNA were tested. The Fa-targeted drug delivery and joint effect of siRNA and TMZ to induce glioma apoptosis and tumor growth inhibition were evaluated both in vitro and in vivo.Results: In vitro cell study demonstrated that the nanocarrier effectively facilitates codelivery of siRNA and TMZ into C6 cells, resulting in a strong apoptotic response of cancer cells by silencing the antiapoptosis BCL-2 gene and activating the proapoptotic Bax gene simultaneously. In vivo study in rat bearing orthotropic glioma showed that tumor growth was inhibited and meanwhile animal survival was prolonged remarkably through intracranial injection of TMZ-FaPEC@siRNA.Conclusion: Our results evidence the strong efficacy of the folate-targeted nanomedicine carrying TMZ and BCL-2 siRNA in treating glioma. Keywords: polymeric nanocarrier, temozolomide, siRNA targeting BCL-2 gene, glioma treatment, drug resistance
format	article
author	Peng Y Huang J Xiao H Wu T Shuai X
author_facet	Peng Y Huang J Xiao H Wu T Shuai X
author_sort	Peng Y
title	Codelivery of temozolomide and siRNA with polymeric nanocarrier for effective glioma treatment
title_short	Codelivery of temozolomide and siRNA with polymeric nanocarrier for effective glioma treatment
title_full	Codelivery of temozolomide and siRNA with polymeric nanocarrier for effective glioma treatment
title_fullStr	Codelivery of temozolomide and siRNA with polymeric nanocarrier for effective glioma treatment
title_full_unstemmed	Codelivery of temozolomide and siRNA with polymeric nanocarrier for effective glioma treatment
title_sort	codelivery of temozolomide and sirna with polymeric nanocarrier for effective glioma treatment
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/03db54d7b5124995b41695c65c87b5d1
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_version_	1718403718504775680

Codelivery of temozolomide and siRNA with polymeric nanocarrier for effective glioma treatment

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