Vasileva Olga, Zaborova Olga, Shmykov Bogdan, Ivanov Roman, Reshetnikov Vasiliy
Translational Medicine Research Center, Sirius University of Science and Technology, Sochi, Russia.
Chemistry Department, Moscow State University, Moscow, Russia.
Front Pharmacol. 2024 Oct 23;15:1466337. doi: 10.3389/fphar.2024.1466337. eCollection 2024.
Today, lipid nanoparticles (LNPs) are some of the main delivery systems for mRNA-based therapeutics. The scope of LNP applications in terms of RNA is not limited to antiviral vaccines but encompasses anticancer drugs and therapeutics for genetic (including rare) diseases. Such widespread use implies high customizability of targeted delivery of LNPs to specific organs and tissues. This review addresses vector-free options for targeted delivery of LNPs, namely the influence of lipid composition of these nanoparticles on their biodistribution. In the review, experimental studies are examined that are focused on the biodistribution of mRNA or of the encoded protein after mRNA administration via LNPs in mammals. We also performed a comprehensive analysis of individual lipids' functional groups that ensure biodistribution to desired organs. These data will allow us to outline prospects for further optimization of lipid compositions of nanoparticles for targeted delivery of mRNA therapeutics.
如今,脂质纳米颗粒(LNPs)是基于mRNA的治疗药物的一些主要递送系统。就RNA而言,LNP的应用范围不仅限于抗病毒疫苗,还包括抗癌药物和用于治疗遗传性(包括罕见)疾病的疗法。如此广泛的应用意味着LNP靶向递送至特定器官和组织具有高度的可定制性。本综述探讨了LNP靶向递送的无载体选择,即这些纳米颗粒的脂质组成对其生物分布的影响。在综述中,我们研究了一些实验研究,这些研究聚焦于通过LNP在哺乳动物体内递送mRNA后,mRNA或编码蛋白的生物分布。我们还对确保向所需器官进行生物分布的单个脂质官能团进行了全面分析。这些数据将使我们能够勾勒出进一步优化纳米颗粒脂质组成以实现mRNA治疗药物靶向递送的前景。