科研之友
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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.
- 出版日期2016-12-10
- 单位东北师范大学; 中国科学院长春应用化学研究所
