Cationic Nanoparticles Assembled from Natural-Based Steroid Lipid for Improved Intracellular Transport of siRNA and pDNA.
Cationic Nanoparticles Assembled from Natural-Based Steroid Lipid for Improved Intracellular Transport of siRNA and pDNA.
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由天然类固醇脂质组装而成的阳离子纳米颗粒可改善 siRNA 和 pDNA 的细胞内运输
DOI：
10.3390/nano6040069
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发表时间：
2016-04-13
期刊：
影响因子：
--
通讯作者：
Zhu JX
中科院分区：
文献类型：
--
作者：
Sheng R;Zhuang X;Wang Z;Cao A;Lin K;Zhu JX
近年来，从生物相容性天然资源中开发用于基因/药物递送的新型功能生物材料引起了越来越多的关注。在这项工作中，我们制备了一系列的阳离子纳米粒子（Diosarg-DOPE纳米粒子）的组装天然类固醇薯蓣皂苷基的阳离子脂质（Diosargg）与商业上可获得的辅助脂质1，2-二油酰基-sn-甘油-3-磷酸乙醇胺（DOPE）。这些阳离子Diosarg-DOPE NP能够通过静电相互作用有效地结合siRNA和质粒DNA（pDNA），以形成稳定的纳米级阳离子脂质纳米颗粒，而不是水溶液中的层状囊泡。检查Diosarg-DOPE NP的siRNA和pDNA复合物的平均粒度、ζ电位和形态。纳米粒的体外细胞毒性取决于Dioblug和DOPE的剂量和组装比例。值得注意的是，通过使用Diosarg-DOPE NPs作为H1299细胞系中的货物，可以大大提高外源siRNA和pDNA的细胞内转运效率。结果表明，自组装Diosarg-DOPE纳米粒对siRNA或pDNA的转运效率明显高于阳离子脂质Diosargg，表明不同功能性脂质组分的协同作用有利于高效纳米基因载体的开发。此外，可以注意到，涉及Dioblug和Diosarg-DOPE NP的细胞内运输的传统“溶酶体定位”，表明辅助脂质DOPE的共组装，可能不会显著影响阳离子脂质的细胞内定位特征。
Developing new functional biomaterials from biocompatible natural-based resources for gene/drug delivery has attracted increasing attention in recent years. In this work, we prepared a series of cationic nanoparticles (Diosarg-DOPE NPs) by assembly of a natural steroid diosgenin-based cationic lipid (Diosarg) with commercially-available helper lipid 1,2-dioleoyl-sn-glycero-3-phosphorethanolamine (DOPE). These cationic Diosarg-DOPE NPs were able to efficiently bind siRNA and plasmid DNA (pDNA) via electrostatic interactions to form stable, nano-sized cationic lipid nanoparticles instead of lamellar vesicles in aqueous solution. The average particle size, zeta potentials and morphologies of the siRNA and pDNA complexes of the Diosarg-DOPE NPs were examined. The in vitro cytotoxicity of NPs depends on the dose and assembly ratio of the Diosarg and DOPE. Notably, the intracellular transportation efficacy of the exogenesis siRNA and pDNA could be greatly improved by using the Diosarg-DOPE NPs as the cargoes in H1299 cell line. The results demonstrated that the self-assembled Diosarg-DOPE NPs could achieve much higher intracellular transport efficiency for siRNA or pDNA than the cationic lipid Diosarg, indicating that the synergetic effect of different functional lipid components may benefit the development of high efficiency nano-scaled gene carriers. Moreover, it could be noted that the traditional “lysosome localization” involved in the intracellular trafficking of the Diosarg and Diosarg-DOPE NPs, indicating the co-assembly of helper lipid DOPE, might not significantly affect the intracellular localization features of the cationic lipids.
影响因子：
5.8
作者：
Huang, Zhaohua;Li, Weijun;Szoka, Francis C., Jr.
通讯作者：
Szoka, Francis C., Jr.