کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8959757 1646351 2018 33 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A novel galactose-PEG-conjugated biodegradable copolymer is an efficient gene delivery vector for immunotherapy of hepatocellular carcinoma
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی بیو مهندسی (مهندسی زیستی)
پیش نمایش صفحه اول مقاله
A novel galactose-PEG-conjugated biodegradable copolymer is an efficient gene delivery vector for immunotherapy of hepatocellular carcinoma
چکیده انگلیسی
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-PegPI/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-γ, 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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomaterials - Volume 184, November 2018, Pages 20-30
نویسندگان
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