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

被引：39

作者：

Tai, Zongguang ^{[1
,2
]}

Ma, Jinyuan ^{[1
]}

Ding, Jianing ^{[1
]}

Pan, Huijun ^{[1
]}

Chai, Rongrong ^{[1
]}

Zhu, Congcong ^{[1
]}

Cui, Zhen ^{[1
]}

Chen, Zhongjian ^{[1
]}

Zhu, Quangang ^{[1
]}

机构：

[1] Tongji Univ, Shanghai Skin Dis Hosp, Sch Med, Baode Rd 1278, Shanghai 200443, Peoples R China

[2] Second Mil Med Univ, Changhai Hosp, Dept Pharm, Shanghai 200433, Peoples R China

来源：

INTERNATIONAL JOURNAL OF NANOMEDICINE | 2020年 / 15卷

基金：

中国国家自然科学基金;

关键词：

long non-coding RNA MEG3; castration-resistant prostate cancer; gene therapy; dendrimer; LONG NONCODING RNA; CYCLIN D1; CELL; PROLIFERATION; P53; DISCOVERIES; MUTATIONS; CARCINOMA; APOPTOSIS; MARKER;

D O I：

10.2147/IJN.S282107

中图分类号：

TB3 [工程材料学];

学科分类号：

0805 ; 080502 ;

摘要：

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.

引用

页码：10305 / 10320

页数：16

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