Aptamer-Functionalized Dendrimer Delivery of Plasmid-Encoding lncRNA MEG3 Enhances Gene Therapy in Castration-Resistant Prostate Cancer

Zongguang Tai,1,2,* Jinyuan Ma,1,* Jianing Ding,1,* Huijun Pan,1 Rongrong Chai,1 Congcong Zhu,1 Zhen Cui,1 Zhongjian Chen,1 Quangang Zhu1 1Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai 200443, People’s Republic of China; 2Department of Pharmacy, Changhai Ho...

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Autores principales:	Tai Z, Ma J, Ding J, Pan H, Chai R, Zhu C, Cui Z, Chen Z, Zhu Q
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	long non-coding rna meg3 castration-resistant prostate cancer gene therapy dendrimer. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/b1336bbd2bec4814b2107a3f7d27965e
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spelling	oai:doaj.org-article:b1336bbd2bec4814b2107a3f7d27965e2021-12-02T15:12:06ZAptamer-Functionalized Dendrimer Delivery of Plasmid-Encoding lncRNA MEG3 Enhances Gene Therapy in Castration-Resistant Prostate Cancer1178-2013https://doaj.org/article/b1336bbd2bec4814b2107a3f7d27965e2020-12-01T00:00:00Zhttps://www.dovepress.com/aptamer-functionalized-dendrimer-delivery-of-plasmid-encoding-lncrna-m-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Zongguang Tai,1,2,* Jinyuan Ma,1,* Jianing Ding,1,* Huijun Pan,1 Rongrong Chai,1 Congcong Zhu,1 Zhen Cui,1 Zhongjian Chen,1 Quangang Zhu1 1Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai 200443, People’s Republic of China; 2Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai 200433, People’s Republic of China*These authors contributed equally to this workCorrespondence: Quangang Zhu; Zhongjian ChenShanghai Skin Disease Hospital, Tongji University School of Medicine, Baode Road 1278, Shanghai 200443, People’s Republic of ChinaTel +86 21 61833155; +86 21 61833007Fax +86 21 61833021Email qgzhu@126.com; aajian818@163.comPurpose: The clinical management of patients with castration-resistant prostate cancer (CRPC) is difficult. However, novel treatment methods are gradually being introduced. Considering the adverse effects of traditional treatments, recent studies have investigated gene therapy as a method to combat CRPC; but, the application of long non-coding (lnc) RNA in gene therapy remains scarce, despite their promise. Therefore, it is imperative to develop a system that can efficiently deliver lncRNA for the treatment of CRPC. Here, we investigated the efficacy of a delivery system by introducing the plasmid-encoding tumor suppressor lncRNA MEG3 (pMEG3) in CRPC cells.Materials and Methods: An EpDT3 aptamer-linked poly(amidoamine) (PAMAM) dendrimer targeting EpCAM was used to deliver pMEG3 in CRPC cells. The PAMAM-PEG-EpDT3/pMEG3 nanoparticles (NPs) were tested using in vitro cellular assays including cellular uptake, entry, and CCK-8 measurement, and tumor growth inhibition, histological assessment, and safety evaluations in in vivo animal models.Results: The EpDT3 aptamer promoted endocytosis of PAMAM and PAMAM-PEG-EpDT3/pMEG3 NPs in CRPC cells. PAMAM-PEG-EpDT3/pMEG3 NPs exhibited a significant anti-CRPC effect, both in vivo and in vitro, when compared to that of unfunctionalized PAMAM-PEG/pMEG3 NPs.Conclusion: PAMAM-PEG-EpDT3/pMEG3 NPs can potentially improve gene therapy in CRPC cells.Keywords: long non-coding RNA MEG3, castration-resistant prostate cancer, gene therapy, dendrimerTai ZMa JDing JPan HChai RZhu CCui ZChen ZZhu QDove Medical Pressarticlelong non-coding rna meg3castration-resistant prostate cancergene therapydendrimer.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 10305-10320 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	long non-coding rna meg3 castration-resistant prostate cancer gene therapy dendrimer. Medicine (General) R5-920
spellingShingle	long non-coding rna meg3 castration-resistant prostate cancer gene therapy dendrimer. Medicine (General) R5-920 Tai Z Ma J Ding J Pan H Chai R Zhu C Cui Z Chen Z Zhu Q Aptamer-Functionalized Dendrimer Delivery of Plasmid-Encoding lncRNA MEG3 Enhances Gene Therapy in Castration-Resistant Prostate Cancer
description	Zongguang Tai,1,2,* Jinyuan Ma,1,* Jianing Ding,1,* Huijun Pan,1 Rongrong Chai,1 Congcong Zhu,1 Zhen Cui,1 Zhongjian Chen,1 Quangang Zhu1 1Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai 200443, People’s Republic of China; 2Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai 200433, People’s Republic of China*These authors contributed equally to this workCorrespondence: Quangang Zhu; Zhongjian ChenShanghai Skin Disease Hospital, Tongji University School of Medicine, Baode Road 1278, Shanghai 200443, People’s Republic of ChinaTel +86 21 61833155; +86 21 61833007Fax +86 21 61833021Email qgzhu@126.com; aajian818@163.comPurpose: The clinical management of patients with castration-resistant prostate cancer (CRPC) is difficult. However, novel treatment methods are gradually being introduced. Considering the adverse effects of traditional treatments, recent studies have investigated gene therapy as a method to combat CRPC; but, the application of long non-coding (lnc) RNA in gene therapy remains scarce, despite their promise. Therefore, it is imperative to develop a system that can efficiently deliver lncRNA for the treatment of CRPC. Here, we investigated the efficacy of a delivery system by introducing the plasmid-encoding tumor suppressor lncRNA MEG3 (pMEG3) in CRPC cells.Materials and Methods: An EpDT3 aptamer-linked poly(amidoamine) (PAMAM) dendrimer targeting EpCAM was used to deliver pMEG3 in CRPC cells. The PAMAM-PEG-EpDT3/pMEG3 nanoparticles (NPs) were tested using in vitro cellular assays including cellular uptake, entry, and CCK-8 measurement, and tumor growth inhibition, histological assessment, and safety evaluations in in vivo animal models.Results: The EpDT3 aptamer promoted endocytosis of PAMAM and PAMAM-PEG-EpDT3/pMEG3 NPs in CRPC cells. PAMAM-PEG-EpDT3/pMEG3 NPs exhibited a significant anti-CRPC effect, both in vivo and in vitro, when compared to that of unfunctionalized PAMAM-PEG/pMEG3 NPs.Conclusion: PAMAM-PEG-EpDT3/pMEG3 NPs can potentially improve gene therapy in CRPC cells.Keywords: long non-coding RNA MEG3, castration-resistant prostate cancer, gene therapy, dendrimer
format	article
author	Tai Z Ma J Ding J Pan H Chai R Zhu C Cui Z Chen Z Zhu Q
author_facet	Tai Z Ma J Ding J Pan H Chai R Zhu C Cui Z Chen Z Zhu Q
author_sort	Tai Z
title	Aptamer-Functionalized Dendrimer Delivery of Plasmid-Encoding lncRNA MEG3 Enhances Gene Therapy in Castration-Resistant Prostate Cancer
title_short	Aptamer-Functionalized Dendrimer Delivery of Plasmid-Encoding lncRNA MEG3 Enhances Gene Therapy in Castration-Resistant Prostate Cancer
title_full	Aptamer-Functionalized Dendrimer Delivery of Plasmid-Encoding lncRNA MEG3 Enhances Gene Therapy in Castration-Resistant Prostate Cancer
title_fullStr	Aptamer-Functionalized Dendrimer Delivery of Plasmid-Encoding lncRNA MEG3 Enhances Gene Therapy in Castration-Resistant Prostate Cancer
title_full_unstemmed	Aptamer-Functionalized Dendrimer Delivery of Plasmid-Encoding lncRNA MEG3 Enhances Gene Therapy in Castration-Resistant Prostate Cancer
title_sort	aptamer-functionalized dendrimer delivery of plasmid-encoding lncrna meg3 enhances gene therapy in castration-resistant prostate cancer
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/b1336bbd2bec4814b2107a3f7d27965e
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Aptamer-Functionalized Dendrimer Delivery of Plasmid-Encoding lncRNA MEG3 Enhances Gene Therapy in Castration-Resistant Prostate Cancer

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