Nanoparticle-mediated tumor cell expression of mIL-12 via systemic gene delivery treats syngeneic models of murine lung cancers.
Nanoparticle-mediated tumor cell expression of mIL-12 via systemic gene delivery treats syngeneic models of murine lung cancers.
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DOI：
10.1038/s41598-021-89124-4
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发表时间：
2021-05-06
影响因子：
4.6
通讯作者：
Minn I
中科院分区：
文献类型：
--
作者：
Ahn HH;Carrington C;Hu Y;Liu HW;Ng C;Nam H;Park A;Stace C;West W;Mao HQ;Pomper MG;Ullman CG;Minn I
肺癌的治疗仍然是临床上的一个关键挑战，基因治疗可以提供有价值的选择。我们描述了一种有效的方法，通过全身注射工程聚合物/DNA纳米粒子介导肿瘤特异性表达的治疗基因，在癌症选择性进展升高基因3（PEG-3）启动子的控制下，治疗患病小鼠肺部的肿瘤。选择临床测试的非靶向聚乙烯亚胺载体以帮助快速过渡到临床研究，并且使用无CpG的质粒骨架和编码序列来减少炎症。在PEG-3启动子的控制下，静脉内施用表达鼠单链白细胞介素12的纳米颗粒显著改善了小鼠在原位和转移性肺癌模型中的存活率，并且没有明显的全身毒性症状。使用临床相关的纳米颗粒组分实现的这些结果提高了转化为人类治疗的前景。
Treatment of cancers in the lung remains a critical challenge in the clinic for which gene therapy could offer valuable options. We describe an effective approach through systemic injection of engineered polymer/DNA nanoparticles that mediate tumor-specific expression of a therapeutic gene, under the control of the cancer-selective progression elevated gene 3 (PEG-3) promoter, to treat tumors in the lungs of diseased mice. A clinically tested, untargeted, polyethylenimine carrier was selected to aid rapid transition to clinical studies, and a CpG-free plasmid backbone and coding sequences were used to reduce inflammation. Intravenous administration of nanoparticles expressing murine single-chain interleukin 12, under the control of PEG-3 promoter, significantly improved the survival of mice in both an orthotopic and a metastatic model of lung cancer with no marked symptoms of systemic toxicity. These outcomes achieved using clinically relevant nanoparticle components raises the promise of translation to human therapy.
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影响因子：
6.2
作者：
Bode C;Zhao G;Steinhagen F;Kinjo T;Klinman DM
通讯作者：
Klinman DM
影响因子：
3.3
作者：
Forde PM;Ettinger DS
通讯作者：
Ettinger DS
影响因子：
5.2
作者：
Eissa IR;Bustos-Villalobos I;Ichinose T;Matsumura S;Naoe Y;Miyajima N;Morimoto D;Mukoyama N;Zhiwen W;Tanaka M;Hasegawa H;Sumigama S;Aleksic B;Kodera Y;Kasuya H
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Kasuya H
影响因子：
46.9
作者：
Lieschke, GJ;Rao, PK;Mulligan, RC
通讯作者：
Mulligan, RC
影响因子：
0.7
作者：
Loi, Monica;Di Paolo, Daniela;Pastorino, Fabio
通讯作者：
Pastorino, Fabio