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改良型纳米颗粒介导的白细胞介素-12 免疫基因治疗结肠癌。

Modified nanoparticle mediated IL-12 immunogene therapy for colon cancer.

机构信息

Department of Neurosurgery and Institute of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, PR China; Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, and West China Hospital, West China Medical School, Sichuan University, Chengdu, PR China.

Department of Neurosurgery and Institute of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, PR China.

出版信息

Nanomedicine. 2017 Aug;13(6):1993-2004. doi: 10.1016/j.nano.2017.04.006. Epub 2017 Apr 18.

Abstract

For the past few years, immunotherapy has recently shown considerable clinical benefit in CRC therapy, and the application of immunologic therapies in cancer treatments continues to increase perennially. Interleukin-12, an ideal candidate for tumor immunotherapy, could activate both innate and adaptive immunities. In this study, we developed a novel gene delivery system with a self-assembly method by MPEG-PLA and DOTAP(DMP) with zeta-potential value of 38.5mV and size of 37.5nm. The supernatant of lymphocytes treated with supernatant from Ct26 transfected pIL12 with DMP could inhibit Ct26 cells growth ex vivo. Treatment of tumor-bearing mice with DMP-pIL12 complex has significantly inhibited tumor growth at both the subcutaneous and peritoneal model in vivo by inhibiting angiogenesis, promoting apoptosis and reducing proliferation. The IL-12 plasmid and DMP complex may be used to treat the colorectal cancer in clinical as a new drug.

摘要

在过去的几年中,免疫疗法最近在 CRC 治疗中显示出相当大的临床益处,免疫疗法在癌症治疗中的应用也在持续增加。白细胞介素-12 是肿瘤免疫治疗的理想候选药物,能够激活先天免疫和适应性免疫。在这项研究中,我们使用 MPEG-PLA 和 DOTAP(DMP)开发了一种具有自组装方法的新型基因传递系统,其 Zeta 电位值为 38.5mV,粒径为 37.5nm。用 DMP 转染 pIL12 的 Ct26 细胞的上清液处理后的淋巴细胞上清液可以在体外抑制 Ct26 细胞的生长。用 DMP-pIL12 复合物治疗荷瘤小鼠,通过抑制血管生成、促进细胞凋亡和减少增殖,在体内皮下和腹腔模型中均显著抑制肿瘤生长。IL-12 质粒和 DMP 复合物可能作为一种新药用于临床治疗结直肠癌。

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