Combined Delivery of Temozolomide and siPLK1 Using Targeted Nanoparticles to Enhance Temozolomide Sensitivity in Glioma

Hui Shi,1,2,* Shuo Sun,1,* Haoyue Xu,3,* Zongren Zhao,3 Zhengzhong Han,3 Jun Jia,3 Dongmei Wu,4 Jun Lu,4 Hongmei Liu,3,5 Rutong Yu1,3,5 1Clinical Medical College, Nanjing Medical University, Nanjing, People’s Republic of China; 2The Second People’s Hospital of Lianyungang, Lianyu...

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Autores principales:	Shi H, Sun S, Xu H, Zhao Z, Han Z, Jia J, Wu D, Lu J, Liu H, Yu R
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	co-delivery polymeric micelle siplk1 tmz drug resistance glioma Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/2e46be38dcc8463ab9cb5915fef8c5c3
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spelling	oai:doaj.org-article:2e46be38dcc8463ab9cb5915fef8c5c32021-12-02T10:26:48ZCombined Delivery of Temozolomide and siPLK1 Using Targeted Nanoparticles to Enhance Temozolomide Sensitivity in Glioma1178-2013https://doaj.org/article/2e46be38dcc8463ab9cb5915fef8c5c32020-05-01T00:00:00Zhttps://www.dovepress.com/combined-delivery-of-temozolomide-and-siplk1-using-targeted-nanopartic-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Hui Shi,1,2,* Shuo Sun,1,* Haoyue Xu,3,* Zongren Zhao,3 Zhengzhong Han,3 Jun Jia,3 Dongmei Wu,4 Jun Lu,4 Hongmei Liu,3,5 Rutong Yu1,3,5 1Clinical Medical College, Nanjing Medical University, Nanjing, People’s Republic of China; 2The Second People’s Hospital of Lianyungang, Lianyungang, People’s Republic of China; 3Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, People’s Republic of China; 4Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu, People’s Republic of China; 5Department of Neurosurgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rutong Yu; Hongmei Liu Tel +86 13182310079; +86 17716228111Email yu.rutong@163.com; liuhongmei816@sina.comIntroduction: Temozolomide (TMZ) is the first-line chemotherapeutic option to treat glioma; however, its efficacy and clinical application are limited by its drug resistance properties. Polo-like kinase 1 (PLK1)-targeted therapy causes G2/M arrest and increases the sensitivity of glioma to TMZ. Therefore, to limit TMZ resistance in glioma, an angiopep-2 (A2)-modified polymeric micelle (A2PEC) embedded with TMZ and a small interfering RNA (siRNA) targeting PLK1 (siPLK1) was developed (TMZ-A2PEC/siPLK).Materials and Methods: TMZ was encapsulated by A2-PEG-PEI-PCL (A2PEC) through the hydrophobic interaction, and siPLK1 was complexed with the TMZ-A2PEC through electrostatic interaction. Then, an angiopep-2 (A2) modified polymeric micelle (A2PEC) embedding TMZ and siRNA targeting polo-like kinase 1 (siPLK1) was developed (TMZ-A2PEC/siPLK).Results: In vitro experiments indicated that TMZ-A2PEC/siPLK effectively enhanced the cellular uptake of TMZ and siPLK1 and resulted in significant cell apoptosis and cytotoxicity of glioma cells. In vivo experiments showed that glioma growth was inhibited, and the survival time of the animals was prolonged remarkably after TMZ-A2PEC/siPLK1 was injected via their tail vein.Discussion: The results demonstrate that the combination of TMZ and siPLK1 in A2PEC could enhance the efficacy of TMZ in treating glioma.Keywords: co-delivery, polymeric micelle, siPLK1, TMZ, drug resistance, gliomaShi HSun SXu HZhao ZHan ZJia JWu DLu JLiu HYu RDove Medical Pressarticleco-deliverypolymeric micellesiplk1tmzdrug resistancegliomaMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 3347-3362 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	co-delivery polymeric micelle siplk1 tmz drug resistance glioma Medicine (General) R5-920
spellingShingle	co-delivery polymeric micelle siplk1 tmz drug resistance glioma Medicine (General) R5-920 Shi H Sun S Xu H Zhao Z Han Z Jia J Wu D Lu J Liu H Yu R Combined Delivery of Temozolomide and siPLK1 Using Targeted Nanoparticles to Enhance Temozolomide Sensitivity in Glioma
description	Hui Shi,1,2,* Shuo Sun,1,* Haoyue Xu,3,* Zongren Zhao,3 Zhengzhong Han,3 Jun Jia,3 Dongmei Wu,4 Jun Lu,4 Hongmei Liu,3,5 Rutong Yu1,3,5 1Clinical Medical College, Nanjing Medical University, Nanjing, People’s Republic of China; 2The Second People’s Hospital of Lianyungang, Lianyungang, People’s Republic of China; 3Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, People’s Republic of China; 4Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu, People’s Republic of China; 5Department of Neurosurgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rutong Yu; Hongmei Liu Tel +86 13182310079; +86 17716228111Email yu.rutong@163.com; liuhongmei816@sina.comIntroduction: Temozolomide (TMZ) is the first-line chemotherapeutic option to treat glioma; however, its efficacy and clinical application are limited by its drug resistance properties. Polo-like kinase 1 (PLK1)-targeted therapy causes G2/M arrest and increases the sensitivity of glioma to TMZ. Therefore, to limit TMZ resistance in glioma, an angiopep-2 (A2)-modified polymeric micelle (A2PEC) embedded with TMZ and a small interfering RNA (siRNA) targeting PLK1 (siPLK1) was developed (TMZ-A2PEC/siPLK).Materials and Methods: TMZ was encapsulated by A2-PEG-PEI-PCL (A2PEC) through the hydrophobic interaction, and siPLK1 was complexed with the TMZ-A2PEC through electrostatic interaction. Then, an angiopep-2 (A2) modified polymeric micelle (A2PEC) embedding TMZ and siRNA targeting polo-like kinase 1 (siPLK1) was developed (TMZ-A2PEC/siPLK).Results: In vitro experiments indicated that TMZ-A2PEC/siPLK effectively enhanced the cellular uptake of TMZ and siPLK1 and resulted in significant cell apoptosis and cytotoxicity of glioma cells. In vivo experiments showed that glioma growth was inhibited, and the survival time of the animals was prolonged remarkably after TMZ-A2PEC/siPLK1 was injected via their tail vein.Discussion: The results demonstrate that the combination of TMZ and siPLK1 in A2PEC could enhance the efficacy of TMZ in treating glioma.Keywords: co-delivery, polymeric micelle, siPLK1, TMZ, drug resistance, glioma
format	article
author	Shi H Sun S Xu H Zhao Z Han Z Jia J Wu D Lu J Liu H Yu R
author_facet	Shi H Sun S Xu H Zhao Z Han Z Jia J Wu D Lu J Liu H Yu R
author_sort	Shi H
title	Combined Delivery of Temozolomide and siPLK1 Using Targeted Nanoparticles to Enhance Temozolomide Sensitivity in Glioma
title_short	Combined Delivery of Temozolomide and siPLK1 Using Targeted Nanoparticles to Enhance Temozolomide Sensitivity in Glioma
title_full	Combined Delivery of Temozolomide and siPLK1 Using Targeted Nanoparticles to Enhance Temozolomide Sensitivity in Glioma
title_fullStr	Combined Delivery of Temozolomide and siPLK1 Using Targeted Nanoparticles to Enhance Temozolomide Sensitivity in Glioma
title_full_unstemmed	Combined Delivery of Temozolomide and siPLK1 Using Targeted Nanoparticles to Enhance Temozolomide Sensitivity in Glioma
title_sort	combined delivery of temozolomide and siplk1 using targeted nanoparticles to enhance temozolomide sensitivity in glioma
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/2e46be38dcc8463ab9cb5915fef8c5c3
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Combined Delivery of Temozolomide and siPLK1 Using Targeted Nanoparticles to Enhance Temozolomide Sensitivity in Glioma

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