Influence of lipid composition of messenger RNA-loaded lipid nanoparticles on the protein expression via intratracheal administration in mice
Influence of lipid composition of messenger RNA-loaded lipid nanoparticles on the protein expression via intratracheal administration in mice
复制标题
信使RNA脂质纳米粒的脂质组成对小鼠气管内给药蛋白表达的影响
DOI：
10.1016/j.ijpharm.2023.122896
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发表时间：
2023
影响因子：
5.8
通讯作者：
Kawakami Shigeru
中科院分区：
文献类型：
--
作者：
Geng Longjian;Kato Naoya;Kodama Yukinobu;Mukai Hidefumi;Kawakami Shigeru
气管内给药利用了呼吸系统的特殊结构，可以有效地将纳米颗粒输送到肺部。关于信使RNA (mRNA)-脂质纳米颗粒（LNPs）的信息管理和脂质组成的影响，还有很多未知。在这项研究中，我们给小鼠气管内注入微量mRNA-LNP溶液，研究脂质组成对肺中蛋白质表达的影响。我们首先验证了mRNA- lnp比mRNA- pei复合物和裸mRNA更高的蛋白表达。然后，我们评估了LNPs的脂质组成对蛋白质表达的影响，发现：1)将PEG的摩尔浓度从1.5%降低到0.5%，可以显著提高蛋白质的表达；2)用DSG-PEG替代DMG-PEG可略微提高蛋白表达；3)用DOPE代替dsc可使蛋白表达提高一个数量级。我们成功制备了具有最佳脂质组成的mRNA-LNP，该mRNA-LNP在给药后具有强大的蛋白表达，从而为治疗性给药mRNA-LNP的高级开发提供了有意义的见解。
Intratracheal (i.t.) administration, which takes advantage of the specific structure of the respiratory system, can effectively deliver nanoparticles to the lung. Much remains unknown about the i.t. administration of messenger RNA (mRNA)-lipid nanoparticles (LNPs) and the effect of lipid composition. In this study, we administered minute amounts of mRNA-LNP solutions into mice intratracheally and investigated the effect of lipid composition on protein expression in the lungs. We first validated higher protein expression with mRNA-LNP compared to that with mRNA-PEI complex and naked mRNA. Then, we evaluated the influence of lipid composition of LNPs on the protein expression and found that: 1) decreasing the PEG molarity from 1.5% to 0.5% could significantly increase the protein expression; 2) replacing DMG-PEG with DSG-PEG could slightly increase the protein expression; 3) using DOPE instead of DSPC could increase protein expression by an order of magnitude. We successfully prepared an mRNA-LNP with optimal lipid compositions that led to robust protein expression following i.t. administration, thus providing meaningful insights into advanced development of mRNA-LNPs for therapeutic i.t. administration.