Modified nanoparticle mediated IL-12 immunogene therapy for colon cancer

Xiaoxiao Liu; Xiang Gao; Songping Zheng; Bilan Wang; Yanyan Li; Chanjuan Zhao; Yagmur Muftuoglu; Song Chen; Ying Li; Haiyan Yao; Hui Sun; Qing Mao; Chao You; Gang Guo; Yuquan Wei

doi:10.1016/j.nano.2017.04.006

Modified nanoparticle mediated IL-12 immunogene therapy for colon cancer

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

Authors

Xiaoxiao Liu¹, Xiang Gao², Songping Zheng³, Bilan Wang⁴, Yanyan Li⁵, Chanjuan Zhao⁴, Yagmur Muftuoglu⁶, Song Chen⁶, Ying Li⁷, Haiyan Yao⁸, Hui Sun⁹, Qing Mao³, Chao You³, Gang Guo³, Yuquan Wei³

Affiliations

¹ 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.
² 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. Electronic address: xiangxianggao2008@163.com.
³ 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.
⁴ Department of Pharmacy, West China Second University Hospital of Sichuan University, Chengdu, PR China.
⁵ Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
⁶ Department of Pharmacology, Yale School of Medicine, Yale University, New Haven, CT, USA.
⁷ Department of Pharmacology, Yale School of Medicine, Yale University, New Haven, CT, USA; Department of Clinical Laboratory, Second Affiliated Hospital of Dalian Medical University, Dalian, China.
⁸ Southern Connecticut State University, New Haven, CT, United States.
⁹ Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, United States.

PMID: 28428054
DOI: 10.1016/j.nano.2017.04.006

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.

Keywords: Colorectal cancer; Immunotherapy; Interleukin-12; Nanoparticles.

MeSH terms

Angiogenesis Inhibitors / administration & dosage*
Angiogenesis Inhibitors / chemistry
Angiogenesis Inhibitors / pharmacology
Animals
Apoptosis / drug effects
Cell Proliferation / drug effects
Colonic Neoplasms / immunology
Colonic Neoplasms / metabolism
Colonic Neoplasms / therapy*
Gene Transfer Techniques*
Genetic Therapy*
Immunotherapy*
Interleukin-12 / administration & dosage*
Interleukin-12 / chemistry
Interleukin-12 / genetics
Interleukin-12 / immunology
Mice
Mice, Inbred BALB C
Nanoparticles / chemistry*
Neovascularization, Pathologic / drug therapy
Neovascularization, Pathologic / immunology
Polyesters / chemistry
Polyethylene Glycols / chemistry
Tumor Cells, Cultured

Substances

Angiogenesis Inhibitors
Polyesters
methoxy poly(ethylene glycol)-poly(lactide)
Interleukin-12
Polyethylene Glycols