...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The journal of physical chemistry, B. Condensed matter, materials, surfaces, interfaces & biophysical >Structure of Lipid Nanoparticles Containing siRNA or mRNA by Dynamic Nuclear Polarization-Enhanced NMR Spectroscopy
【24h】

Structure of Lipid Nanoparticles Containing siRNA or mRNA by Dynamic Nuclear Polarization-Enhanced NMR Spectroscopy

机译：通过动态核偏振增强的NMR光谱含有siRNA或mRNA的脂质纳米颗粒的结构

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Here, we show how dynamic nuclear polarization (DNP) NMR spectroscopy experiments permit the atomic level structural characterization of loaded and empty lipid nanoparticles (LNPs). The LNPs used here were synthesized by the microfluidic mixing technique and are composed of ionizable cationic lipid (DLin-MC3-DMA), a phospholipid (distearoylphosphatidylcholine, DSPC), cholesterol, and poly(ethylene glycol) (PEG) (dimyristoyl phosphatidyl ethanolamine (DMPE) PEG 2000), as well as encapsulated cargoes that are either phosphorothioated siRNA (50 or 100%) or mRNA. We show that LNPs form physically stable complexes with bioactive drug siRNA for a period of 94 days. Relayed DNP experiments are performed to study H-1-H-1 spin diffusion and to determine the spatial location of the various components of the LNP by studying the average enhancement factors as a function of polarization time. We observe a striking feature of LNPs in the presence and in the absence of encapsulating siRNA or mRNA by comparing our experimental results to numerical spin-diffusion modeling. We observe that LNPs form a layered structure, and we detect that DSPC and DMPE-PEG 2000 lipids form a surface rich layer in the presence (or absence) of the cargoes and that the cholesterol and ionizable cationic lipid are embedded in the core. Furthermore, relayed DNP 31P solid-state NMR experiments allow the location of the cargo encapsulated in the LNPs to be determined. On the basis of the results, we propose a new structural model for the LNPs that features a homogeneous core with a tendency for layering of DSPC and DMPE PEG at the surface.
机译：在这里，我们展示了动态核偏振（DNP）NMR光谱实验如何允许装载和空脂质纳米颗粒（LNP）的原子水平结构表征。这里使用的LNP通过微流体混合技术合成，并且由可电离的阳离子脂质（DIN-MC3-DMA），磷脂（Distearoylphollylcholine，DSPC），胆固醇和聚（乙二醇）（PEG）（Divyristoyl磷脂酰乙醇胺（ DMPE）PEG 2000），以及透明的货物，其是磷化噻嗪类siRNA（50或100％）或mRNA。我们表明LNPS形成与生物活性药物siRNA的物理稳定的复合物，为94天。进行转发的DNP实验以研究H-1-H-1自旋扩散，并通过研究作为偏振时间的函数的平均增强因子来确定LNP各种组分的空间位置。通过将我们的实验结果与数值自旋扩散建模的比较，我们观察在存在和没有封装siR​​NA或mRNA的情况下的LNP的显着特征。我们观察到LNP形成分层结构，我们检测到DSPC和DMPE-PEG 2000脂质在货物的存在（或不存在）中形成表面富含层，并且胆固醇和可电离的阳离子脂质嵌入核心中。此外，中继DNP 31P固态NMR实验允许确定封装在LNP中的货物的位置。在结果的基础上，我们为LNP提出了一种新的结构模型，其具有均匀核心，其倾向于在表面倾向于分层DSPC和DMPE PEG。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号