The role of the helper lipid on the DNA transfection efficiency of lipopolyplex formulations.
The role of the helper lipid on the DNA transfection efficiency of lipopolyplex formulations.
复制标题
辅助脂质对脂多复合物制剂 DNA 转染效率的作用。
DOI：
10.1038/srep07107
复制
发表时间：
2014-11-19
影响因子：
4.6
通讯作者：
Hart SL
中科院分区：
文献类型：
--
作者：
Du Z;Munye MM;Tagalakis AD;Manunta MD;Hart SL
由阳离子脂质体和阳离子受体靶向多肽的混合物组成的多功能脂多糖制剂在基因治疗应用中具有潜在的用途。这里所述的脂多糖制剂通常比二元脂复合体或复合制剂更有效的转染剂。以前已经表明，多肽成分既介导了DNA包装，也介导了纳米颗粒的靶向，而在本报告中，我们研究了脂质成分的贡献。我们假设，在脂类双层融合后，脂类成分与多肽在转染过程中通过促进内体逃逸而协同作用。用含有DOTAP和中性脂类或DOPC的阳离子脂质体制备脂多合物。DOPC促进融合、倒置的六角形脂肪结构，而DOPC促进更稳定的层状结构。无论是在体内还是体外，含有药物的脂多聚物的转染率都显著高于含有DOPC的脂多聚体。含有DOPE的脂多糖显示出DNA的快速内体转运和核积聚，而含有DOPC的制剂仍然留在晚期的内切酶体内。这些发现与之前关于药物在脂复合物中的作用的发现是一致的，并支持关于脂质体中脂成分功能的假设。这些发现将有助于为未来的脂多糖设计、策略和临床开发过程提供信息。
Multifunctional, lipopolyplex formulations comprising a mixture of cationic liposomes and cationic, receptor-targeting peptides have potential use in gene therapy applications. Lipopolyplex formulations described here are typically far more efficient transfection agents than binary lipoplex or polyplex formulations. It has been shown previously that the peptide component mediates both DNA packaging and targeting of the nanoparticle while in this report we investigate the contribution of the lipid component. We hypothesised that the lipid components synergise with the peptides in the transfection process by promoting endosomal escape after lipid bilayer fusion. Lipopolyplexes were prepared with cationic liposomes comprising DOTAP with either neutral lipid DOPE or DOPC. DOPE promotes fusogenic, inverted hexagonal lipid structures while DOPC promotes more stable laminar structures. Lipopolyplexes containing DOPE showed substantially higher transfection efficiency than those formulated with DOPC, both in vitro and in vivo. DOPE-containing lipopolyplexes showed rapid endosomal trafficking and nuclear accumulation of DNA while DOPC-containing formulations remained within the late endo-lysosomal compartments. These findings are consistent with previous finding for the role of DOPE in lipoplexes and support the hypothesis regarding the function of the lipid components in lipopolyplexes. These findings will help to inform future lipopolyplex design, strategies and clinical development processes.
登录
查看更多内容
影响因子：
4.2
作者：
Hart, SL;Arancibia-Cárcamo, CV;Kinnon, C
通讯作者：
Kinnon, C
影响因子：
10.8
作者：
Koh, Chee Guan;Zhang, Xulang;Liu, Shujun;Golan, Sharon;Yu, Bo;Yang, Xiaojuan;Guan, Jingjiao;Jin, Yan;Talmon, Yeshayahu;Muthusamy, Natarajan;Chan, Kenneth K.;Byrd, John C.;Lee, Robert J.;Marcucci, Guido;Lee, L. James
通讯作者：
Lee, L. James
阳离子脂质包被的 PEI/DNA 复合物可提高基因递送至间充质干细胞的效率并降低细胞毒性
影响因子：
8
作者：
Song H;Wang G;He B;Li L;Li C;Lai Y;Xu X;Gu Z
通讯作者：
Gu Z
影响因子：
7.3
作者：
Caracciolo, Giulio;Pozzi, Daniela;Lagana, Aldo
通讯作者：
Lagana, Aldo
影响因子：
14
作者：
Tagalakis, Aristides D.;Grosse, Stephanie M.;Hart, Stephen L.
通讯作者：
Hart, Stephen L.