Shen Zhigao, Liu Cong, Wang Ziqian, Xie Fengfei, Liu Xingwu, Dong Lingkai, Pan Xuehua, Zeng Chen, Wang Peng George
Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China.
Pharmaceutics. 2023 Feb 1;15(2):477. doi: 10.3390/pharmaceutics15020477.
Lipid nanoparticles (LNPs) are the commonly used delivery tools for messenger RNA (mRNA) therapy and play an indispensable role in the success of COVID-19 mRNA vaccines. Ionizable cationic lipids are the most important component in LNPs. Herein, we developed a series of new ionizable lipids featuring bioreducible disulfide bonds, and constructed a library of lipids derived from dimercaprol. LNPs prepared from these ionizable lipids could be stored at 4 °C for a long term and are non-toxic toward HepG2 and 293T cells. In vivo experiments demonstrated that the best C4S18A formulations, which embody linoleoyl tails, show strong firefly luciferase (Fluc) mRNA expression in the liver and spleen via intravenous (IV) injection, or at the local injection site via intramuscular injection (IM). The newly designed ionizable lipids can be potentially safe and high-efficiency nanomaterials for mRNA therapy.
脂质纳米颗粒（LNPs）是信使核糖核酸（mRNA）疗法常用的递送工具，在新冠病毒mRNA疫苗的成功研发中发挥了不可或缺的作用。可电离阳离子脂质是LNPs中最重要的成分。在此，我们开发了一系列具有生物可还原二硫键的新型可电离脂质，并构建了一个源自二巯丙醇的脂质文库。由这些可电离脂质制备的LNPs可以在4℃长期储存，并且对HepG2和293T细胞无毒。体内实验表明，体现亚油酰基尾部的最佳C4S18A制剂，通过静脉注射（IV）或肌肉注射（IM）在局部注射部位，在肝脏和脾脏中显示出强烈的萤火虫荧光素酶（Fluc）mRNA表达。新设计的可电离脂质有可能成为用于mRNA治疗的安全高效纳米材料。
