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

• Main Authors: Tai Z, Ma J, Ding J, Pan H, Chai R, Zhu C, Cui Z, Chen Z, Zhu Q
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-12-01
• Series: International Journal of Nanomedicine
• Subjects: long non-coding rna meg3; castration-resistant prostate cancer; gene therapy; dendrimer.
• Online Access: https://www.dovepress.com/aptamer-functionalized-dendrimer-delivery-of-plasmid-encoding-lncrna-m-peer-reviewed-article-IJN
• ISSN: 1178-2013

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 [phone]; [phone]Fax [phone]Email [e-mail]; [e-mail]: 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