Aptamer-Functionalized Dendrimer Delivery of Plasmid-Encoding lncRNA MEG3 Enhances Gene Therapy in Castration-Resistant Prostate Cancer
Authors Tai Z, Ma J, Ding J, Pan H, Chai R, Zhu C, Cui Z, Chen Z, Zhu Q
Received 18 September 2020
Accepted for publication 30 November 2020
Published 17 December 2020 Volume 2020:15 Pages 10305—10320
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Farooq A. Shiekh
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 Zhu 1
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 work
Correspondence: Quangang Zhu; Zhongjian Chen
Shanghai Skin Disease Hospital, Tongji University School of Medicine, Baode Road 1278, Shanghai 200443, People’s Republic of China
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Purpose: 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
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