A novel phosphoester-based cationic co-polymer nanocarrier delivers chimeric antigen receptor plasmid and exhibits anti-tumor effect†,RSC Advances

当前位置： X-MOL 学术 › RSC Adv. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

A novel phosphoester-based cationic co-polymer nanocarrier delivers chimeric antigen receptor plasmid and exhibits anti-tumor effect†
RSC Advances ( IF 3.9 ) Pub Date : 2018-04-19 00:00:00 , DOI: 10.1039/c8ra02133c
Jing Fan _{1,

2} , Qianjun He ₃ , Zhaokui Jin ₃ , Wei Chen ₁ , Weiren Huang ₁

Affiliation

Chimeric antigen receptor T cells (CAR-T cells) targeting of CD19 antigen has been proven to be effective and successful in B cell acute lymphoblastic leukemia. The traditional CAR delivery systems have several problems such as poor biosafety, low loading capacity, and low transfection efficiency. Utilization of nanocarriers for CAR delivery offers new possibilities for CAR-T treatment. In the present study, an anti-CD19 CAR expression lentivirus plasmid was constructed for CAR delivery and immunotherapy. In addition, a three-segment amphiphilic co-polymer, methoxy polyethylene glycol-branched polyethyleneimine-poly(2-ethylbutyl phospholane) (mPEG-bPEI-PEBP) was synthesized via click reaction as the carrier with cationic PEI, capable of delivering the CAR and packaging plasmids to co-transfect Jurkat cells and undergo expression. The PEBP and mPEG parts of the co-polymer provide hydrophobic and hydrophilic interfaces and lead to the co-polymer self-assembly into micelles in water and encapsulation of the DNA plasmids. The mPEG-bPEI-PEBP-DNA composites with different N/P ratios were incubated with the CD19 overexpression K562 cells to identify the CAR functions. The obtained CAR-Jurkat cells had the ability to secrete interferon-γ and interleukin-2. The cytotoxic effects to CD19-K562 cells suggest that the induced CAR-Jurkat cells have an excellent targeted antitumor activity.

中文翻译：

一种基于磷酸酯的新型阳离子共聚物纳米载体可传递嵌合抗原受体质粒并具有抗肿瘤作用†

靶向 CD19 抗原的嵌合抗原受体 T 细胞（CAR-T 细胞）已被证明在 B 细胞急性淋巴细胞白血病中是有效和成功的。传统的CAR传递系统存在生物安全性差、载量低、转染效率低等问题。利用纳米载体进行 CAR 递送为 CAR-T 治疗提供了新的可能性。在本研究中，构建了一种抗 CD19 CAR 表达慢病毒质粒，用于 CAR 递送和免疫治疗。此外，通过以下方法合成了三段两亲共聚物甲氧基聚乙二醇支化聚乙烯亚胺-聚（2-乙基丁基膦）（mPEG-bPEI-PEBP）以阳离子PEI为载体的click反应，能够将CAR和包装质粒共转染Jurkat细胞并进行表达。共聚物的 PEBP 和 mPEG 部分提供疏水和亲水界面并导致共聚物在水中自组装成胶束并封装 DNA 质粒。将具有不同 N/P 比的 mPEG-bPEI-PEBP-DNA 复合物与 CD19 过表达 K562 细胞一起孵育以鉴定 CAR 功能。获得的CAR-Jurkat细胞具有分泌干扰素-γ和白细胞介素-2的能力。对CD19-K562细胞的细胞毒作用表明诱导的CAR-Jurkat细胞具有优异的靶向抗肿瘤活性。

更新日期：2018-04-19

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11