聚乙烯亚胺
胶质瘤
转染
基因传递
自杀基因
病毒载体
血脑屏障
化学
癌症研究
遗传增强
聚赖氨酸
纳米医学
体内
药理学
生物
生物化学
材料科学
基因
纳米技术
中枢神经系统
生物技术
纳米颗粒
神经科学
重组DNA
作者
Shiqian Gao,Huayu Tian,Zhenkai Xing,Dawei Zhang,Yifeng Guo,Zhaopei Guo,Xuemei Zhu,Xuesi Chen
标识
DOI:10.1016/j.jconrel.2016.10.027
摘要
Herpes simplex virus type I thymidine kinase gene (HSV-TK) in viral vector is a promising strategy against glioblastoma multiforme (GBM). However, the biosafety risk restricts its application in clinic. In this work, poly (l-lysine)-grafted polyethylenimine (PEI-PLL), which combines the high transfection efficiency of polyethylenimine and the good biodegradability of poly (l-lysine), was adopted as the non-viral vector backbone. Angiopep-2, a blood brain barrier (BBB) crossing and glioma targeting bifunctional peptide was conjugated on PEI-PLL via polyethyleneglycol (PEG) and designated as PPA. The optimal transfection ratio of PPA/DNA complexes nanoparticles (PPA NPs) was firstly characterized. Next, the glioma targeting of the PPA NPs was confirmed through cellular uptake and transfection analysis. The in vivo imaging studies demonstrated that the PPA NPs could not only penetrate BBB but also accumulate in striatum and cortex via systemic administration. Moreover, the PPA/HSV-TK NPs showed remarkably anti-glioma effect and survival benefit in an invasive orthotopic human GBM mouse model through inhibiting proliferation and inducing apoptosis (p < 0.05 vs control). This study firstly illustrated that the cationic polymer PPA could be exploited as an efficient gene vector to cross the BBB, and innovatively provided a potential non-viral nanomedicine for noninvasive suicide gene therapy in the glioma treatment.
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