Recent advances in nonviral vectors for gene delivery.
Recent advances in nonviral vectors for gene delivery.
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DOI：
10.1021/ar200151m
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发表时间：
2012-07-17
影响因子：
18.3
通讯作者：
Huang, Leaf
中科院分区：
文献类型：
--
作者：
Guo, Xia;Huang, Leaf
由于病毒载体的安全性考虑，通常基于阳离子脂类或聚合物的非病毒载体是首选的。到目前为止，非病毒载体可以熟练地在培养细胞中转染细胞，但获得有效的纳米药物还远远不明显。克服与非病毒载体相关的障碍对于提高核酸的输送效率和治疗效果具有重要意义。这些缺点包括阳离子载体与血液成分的强相互作用、被网状内皮系统(RES)摄取、毒性、载体对目标细胞的靶向能力等。聚乙二醇化是静脉给药后减少血浆蛋白与非病毒载体结合和减少RES清除的主要方法。由于渗透性和滞留效应的增强，没有迅速从循环中清除的纳米颗粒在肿瘤中积累，附着在聚乙二醇化成分远端的靶向配体允许与靶细胞表面的受体结合。中性或阴离子脂质体也已被开发出来，用于在实验动物模型中全身递送核酸。设计和合成新型阳离子脂类和聚合物，将核酸与多肽、靶向配体、聚合物或环境敏感部分结合起来，也引起了人们对非病毒载体所面临的问题的关注。无机纳米颗粒在核酸输送中的应用也是一个新兴的领域。最近，不同类别的非病毒载体似乎正在融合，不同类别的非病毒载体的特征可以结合在一个策略中。因此，与高效核酸输送相关的更多障碍可能会被克服。在这篇文章中，我们将重点介绍这些新型的非病毒载体，它们分为多功能杂化核酸载体、新型膜/核核酸载体和超声响应型核酸载体。重点介绍了系统性递送研究。最后，对核酸递送的前景进行了展望。我们认为，更好地了解纳米颗粒在细胞内的命运以及杂化颗粒各部分之间的相互作用将导致适合临床使用的递送系统。我们还强调了核酸持续释放的价值，并推测以体内持续释放的细胞为靶点的载体应该是一个有趣的研究挑战。
Non-viral vectors, typically based on cationic lipids or polymers, are preferred due to safety concerns with viral vectors. So far, non-viral vectors can proficiently transfect cells in culture, but obtaining efficient nanomedicines is far from evident. To overcome the hurdles associated with non-viral vectors is significant for improving delivery efficiency and therapeutic effect of nucleic acid. The drawbacks include the strong interaction of cationic delivery vehicles with blood components, uptake by the reticuloendothelial system (RES), toxicity, targeting ability of the carriers to the cells of interest, and so on. PEGylation is the predominant method used to reduce the binding of plasma proteins with non-viral vectors and minimize the clearance by RES after intravenous administration. The nanoparticles that are not rapidly cleared from the circulation accumulate in the tumors due to the enhanced permeability and retention effect, and the targeting ligands attached to the distal end of the PEGylated components allow binding to the receptors on the target cell surface. Neutral or anionic liposomes have been also developed for systemic delivery of nucleic acids in experimental animal model. Designing and synthesizing novel cationic lipids and polymers, and binding nucleic acid with peptides, targeting ligands, polymers, or environmentally sensitive moieties also attract many attentions for resolving the problems encountered by non-viral vectors. The application of inorganic nanoparticles in nucleic acid delivery is an emerging field, too. Recently, different classes of non-viral vectors appear to be converging and the features of different classes of non-viral vectors could be combined in one strategy. More hurdles associated with efficient nucleic acid delivery therefore might be expected to be overcome. In this account, we will focus on these novel non-viral vectors, which are classified into multifunctional hybrid nucleic acid vectors, novel membrane/core nanoparticles for nucleic acid delivery and ultrasound-responsive nucleic acid vectors. The systemic delivery studies are highlighted. Finally, we bring forward the prospect for nucleic acid delivery. We think a better understandings of the fate of the nanoparticles inside the cell and of the interactions between the parts of hybrid particles will lead to a delivery system suitable for clinical use. We also underscore the value of sustained release of nucleic acid and presume making vectors targeted to cells with sustained release in vivo should be an interesting research challenge.
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影响因子：
4.9
作者：
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通讯作者：
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通讯作者：
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