A novel galactose-PEG-conjugated biodegradable copolymer is an efficient gene delivery vector for immunotherapy of hepatocellular carcinoma

作者：Liu, Ling; Zong, Zhi-Min^*; Liu, Qian; Jiang, Shuang-Shuang; Zhang, Qian; Cen, Lan-Qi; Gao, Jian; Gao, Xiao-Ge; Huang, Jian-Dong; Liu, Yi; Yao, Hong^*

来源：Biomaterials, 2018, 184: 20-30.

DOI：10.1016/j.biomaterials.2018.08.064

• Polyethylenimine
• Galactose
• Liver target
• IL15
• Immunogene therapy

Successful immunogene therapy depends not only on the therapeutic gene but also on the gene delivery vector. In this study, we synthesized a novel copolymer consisting of low-molecular-weight polyethylenimine (PEI) cross-linked by myo-inositol (INO) and conjugated with a galactose-grafted PEG chain, named LA-PegPI. We characterized the chemical structure and molecular weight of the copolymer and particle properties of LA-PegPI/pDNA. Furthermore, we showed that LA-PegPl/pDNA polyplexes possessed excellent stability in physiological salt solution, low cytotoxicity,.and high transfection efficiency in the asialoglycoprotein receptor (ASGPR)-positive liver cells in vitro. Importantly, we also showed that through intraperitoneal injection of LA-PegPI/pDNA nanoparticles, the reporter gene was forcefully expressed in the liver hepatocytes of mice. Finally, we documented that intraperitoneal injection of LA-PegPI/pIL15 nanoparticles effectively suppressed tumor growth and prolonged survival time of tumor-bearing mice via activation of CD8(+) T cells and NK cells and upregulation of the cytokines IFN-gamma, TNF, and IL12 in an orthotopic hepatocellular carcinoma mouse model. Interestingly, LA-PegPI/pluc nanoparticles could effectively stimulate the proliferation of NK cells and inhibit tumor growth in this model. In summary, LA-PegPI is a useful gene vector for immunogene therapy of hepatocellular carcinoma, and its potential for clinical application warrants further study.

• 出版日期2018-11
• 单位中国科学院; 香港大学深圳研究院; 徐州医科大学; 香港中文大学; 中国矿业大学（北京）; 中国科学院深圳先进技术研究院