Modified nanoparticle mediated IL-12 immunogene therapy for colon cancer

被引:56
作者
Liu, Xiaoxiao [1 ,2 ,3 ,9 ,10 ]
Gao, Xiang [1 ,2 ,3 ]
Zheng, Songping [1 ,2 ,3 ]
Wang, Bilan [4 ]
Li, Yanyan [8 ]
Zhao, Chanjuan [4 ]
Muftuoglu, Yagmur [5 ]
Chen, Song [5 ]
Li, Ying [5 ,11 ]
Yao, Haiyan [6 ]
Sun, Hui [7 ]
Mao, Qing [1 ,2 ,3 ]
You, Chao [1 ,2 ,3 ]
Guo, Gang [1 ,2 ,3 ]
Wei, Yuquan [1 ,2 ,3 ]
机构
[1] Sichuan Univ, West China Med Sch, West China Hosp, Dept Neurosurg, Chengdu, Sichuan, Peoples R China
[2] Sichuan Univ, West China Med Sch, West China Hosp, Inst Neurosurg,State Key Lab Biotherapy, Chengdu, Sichuan, Peoples R China
[3] Collaborat Innovat Ctr Biotherapy, Chengdu, Sichuan, Peoples R China
[4] Sichuan Univ, West China Univ Hosp 2, Dept Pharm, Chengdu, Sichuan, Peoples R China
[5] Yale Univ, Yale Sch Med, Dept Pharmacol, New Haven, CT USA
[6] Southern Connecticut State Univ, New Haven, CT 06515 USA
[7] Yale Univ, Sch Med, Dept Microbial Pathogenesis, New Haven, CT USA
[8] Fudan Univ, Shanghai Canc Ctr, Dept Radiat Oncol, Shanghai, Peoples R China
[9] Sichuan Univ, Dept Med Oncol, Canc Ctr,West China Med Sch, State Key Lab Biotherapy,Collaborat Innovat Ctr B, Chengdu, Sichuan, Peoples R China
[10] Sichuan Univ, West China Med Sch, West China Hosp, Chengdu, Sichuan, Peoples R China
[11] Dalian Med Univ, Dept Clin Lab, Affiliated Hosp 2, Dalian, Peoples R China
基金
中国国家自然科学基金;
关键词
Colorectal cancer; Immunotherapy; Interleukin-12; Nanoparticles; GENE-THERAPY; TNF-ALPHA; T-CELLS; INTERFERON-GAMMA; IN-VIVO; INTERLEUKIN-12; LYMPHOCYTES; DELIVERY; IMMUNOTHERAPY; ANGIOGENESIS;
D O I
10.1016/j.nano.2017.04.006
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
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 38.5 mV and size of 37.5 nm. 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 DMPpIL12 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. (C) 2017 Elsevier Inc. All rights reserved.
引用
收藏
页码:1993 / 2004
页数:12
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