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首页> 外文期刊>RSC Advances >A novel phosphoester-based cationic co-polymer nanocarrier delivers chimeric antigen receptor plasmid and exhibits anti-tumor effect
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A novel phosphoester-based cationic co-polymer nanocarrier delivers chimeric antigen receptor plasmid and exhibits anti-tumor effect

机译：一种新型的基于磷酸酯的阳离子共聚物纳米载体可提供嵌合抗原受体质粒并具有抗肿瘤作用

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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.
机译：已经证明靶向CD19抗原的嵌合抗原受体T细胞（CAR-T细胞）在B细胞急性淋巴细胞白血病中是有效的。传统的CAR输送系统存在一些问题，例如生物安全性差，负载能力低和转染效率低。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，构建了抗CD19 CAR表达慢病毒质​​粒用于CAR递送和免疫治疗。此外，通过点击反应合成了三段两亲共聚物，即甲氧基聚乙二醇支化的聚乙烯亚胺-聚（2-乙基丁基膦酸酯）（mPEG-bPEI-PEBP）作为带有阳离子PEI的载体，能够传递CAR并包装质粒以共转染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包裹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和白介素-2的能力。对CD19-K562细胞的细胞毒性作用表明，诱导的CAR-Jurkat细胞具有出色的靶向抗肿瘤活性。

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