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M-PEIs nanogels: potential nonviral vector for systemic plasmid delivery to tumor cells

机译:M-PEIs纳米凝胶:潜在的非病毒载体,可用于全身性质粒递送至肿瘤细胞

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Successfully systemic gene therapy has been hindered by vector-related limitations, including toxicity and inefficient gene delivery to tumor cells after intravenous administration. In this study, we evaluated the potential of spherical polyethylenimine nanogels (M-PEIs) as a novel vector for intravenous delivery of plasmids to tumor cells. M-PEIs provided a sustained release of plasmids up to 14 days and were also effective in protecting plasmids from enzymatic degradation in serum-conditioned media. M-PEIs showed no obvious cytotoxicity to mammalian cells in vitro as well as to liver, heart and kidney in mice after intravenous injection. Importantly, following intravenous administration of M-PEIs/plasmid complexes into human hepatocellular carcinoma xenograft-bearing mice, green fluorescence protein reporter gene expression was predominantly found in the tumor. This study indicates that M-PEIs may be a candidate for systemic delivery of plasmids into tumors.
机译:载体相关的局限性阻碍了成功的全身基因治疗,包括毒性和静脉内给药后向肿瘤细胞的无效基因传递。在这项研究中,我们评估了球形聚乙烯亚胺纳米凝胶(M-PEI)作为将质粒静脉内递送至肿瘤细胞的新型载体的潜力。 M-PEI提供了长达14天的质粒持续释放,并且在保护质粒免受血清条件培养基中的酶促降解方面也很有效。静脉注射后,M-PEI对小鼠的哺乳动物细胞以及肝脏,心脏和肾脏均无明显的细胞毒性。重要的是,在将M-PEI /质粒复合物静脉内给药于人肝癌异种移植小鼠后,主要在肿瘤中发现了绿色荧光蛋白报告基因的表达。这项研究表明,M-PEIs可能是将质粒全身递送至肿瘤的候选药物。

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