Self-Assembly of a Multifunctional Lipid With Core-Shell Dendrimer DNA Nanoparticles Enhanced Efficient Gene Delivery at Low Charge Ratios into RPE Cells.
Self-Assembly of a Multifunctional Lipid With Core-Shell Dendrimer DNA Nanoparticles Enhanced Efficient Gene Delivery at Low Charge Ratios into RPE Cells.
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DOI：
10.1002/mabi.201500192
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发表时间：
2015-12
影响因子：
4.6
通讯作者：
Lu ZR
中科院分区：
文献类型：
--
作者：
Sun D;Maeno H;Gujrati M;Schur R;Maeda A;Maeda T;Palczewski K;Lu ZR
基因治疗是治疗遗传性疾病的一种很有前途的方法。开发高效、低毒的基因传递系统是基因治疗临床应用的重点。在这项工作中，我们设计并评估了一种混合非病毒基因递送系统，该系统由多功能脂质ECO和核壳树状聚合物G4纳米球组成，用于在低电荷比（N/P）下有效的细胞内基因递送。设计树枝状聚合物纳米球以有效地浓缩基因货物，并且使用阳离子脂质来增强细胞摄取。正如预期的那样，该混合系统在低N/P比（总N/P = 6）下形成稳定的纳米颗粒，并且具有低细胞毒性。在低N/P比下，在含有10%血清的培养基中，杂交纳米颗粒诱导ARPE-19细胞中GFP（绿色荧光蛋白）表达高于无血清培养基。纳米颗粒还介导了野生型C57小鼠离体视网膜和BALB/c小鼠体内视网膜中显著的报告基因GFP表达。总之，这些结果表明，合理设计的G4纳米球/pDNA/ECO纳米颗粒是一种有前途的递送系统，用于在低电荷比的体外和体内基因递送。
Gene therapy is a promising approach to treat genetic diseases. Development of gene delivery systems with high efficiency and low toxicity is a high priority in clinical application of gene therapy. In this work, we designed and evaluated a hybrid nonviral gene delivery system composed of a multifunctional lipid ECO and a core-shell dendrimer G4 nanoglobule for efficient intracellular gene delivery at low charge ratios (N/P). The dendrimeric nanoglobule was designed to effectively condense the gene cargo and the cationic lipid was used to enhance cellular uptake. As expected, this hybrid system formed stable nanoparticles at low N/P ratios (overall N/P = 6) and had low cytotoxicity. The hybrid nanoparticles induced higher GFP (green fluorescent protein) expression in ARPE-19 cells in the culture medium containing 10% serum than in serum-free medium at low N/P ratios. The nanoparticles also mediated significant reporter gene GFP expression in the retina ex-vivo from wild type C57 mice and in vivo with BALB/c mice. Together, these results demonstrate that the rationally designed G4 nanoglobule/pDNA/ECO nanoparticles are a promising delivery system for in vitro and in vivo gene delivery at low charge ratios.