LNP-mRNA递送系统靶向治疗肺部疾病的研究进展  

Research Advances in Targeted Therapy of Pulmonary Diseases Using the LNP-mRNA Delivery System

作　　者：杨智聪 王尚志 梁玉雪 张颖颖 YANG Zhicong;WANG Shangzhi;LIANG Yuxue;ZHANG Yingying(School of Pharmacy,Shandong University of Traditional Chinese Medicine,Jinan 250355,China;College of Traditional Chinese Medicine,Shandong University of Traditional Chinese Medicine,Jinan 250355,China)

机构地区：[1]山东中医药大学药学院,济南250355 [2]山东中医药大学中医学院,济南250355

出　　处：《中国生物工程杂志》2025年第2期54-67,共14页China Biotechnology

基　　金：山东省科技厅山东省重点研发项目(2022CXGC020514);山东省科技型中小企业创新能力提升项目(2022TSGC2593)资助项目。

摘　　要：脂质纳米颗粒(lipid nanoparticles,LNPs)是一类由脂质分子组成的纳米级载体,通常包括可离子化脂质(Ionizable lipids)、磷脂(phospholipids)、胆固醇(cholesterol)以及聚乙二醇化脂质(PEGylated lipids)四种关键成分,用于包裹和保护mRNA分子,以确保其在体内的稳定性和有效递送。LNP-mRNA递送系统,即脂质纳米颗粒介导的mRNA技术,作为mRNA的高效递送工具,在肺部疾病治疗上已经展现出巨大的应用前景。近年来,随着COVID-19疫苗的成功应用,LNP-mRNA技术得到了快速发展和广泛关注。综述了LNP-mRNA递送系统在不同肺部疾病治疗中的研究进展,包括其设计原理、优化策略、体内外试验结果及临床应用前景。特别关注了LNPs的靶向性以及在治疗肺遗传性疾病、感染性疾病和肺癌等方面的应用。此外,还讨论了当前面临的挑战和未来的发展方向,为LNP-mRNA技术在肺部疾病治疗中的应用提供了科学依据和策略指导。Lipid nanoparticles(LNPs),nanoscale delivery vehicles composed of lipid molecules,are distinguished by four major components:ionizable lipids,phospholipids,cholesterol,and lipids conjugated with polyethylene glycol(PEG).These components work in synergy to encapsulate and protect mRNA molecules,ensuring their integrity and facilitating their effective transport throughout the body.The LNP-mRNA delivery mechanism,which utilizes the encapsulation of messenger RNA by lipid nanoparticles,has emerged as a promising therapeutic modality for pulmonary diseases.The emergence and success of COVID-19 vaccines has driven the development and recognition of this technology.This review discusses advances in the application of LNP-mRNA system to treat a spectrum of pulmonary diseases.It includes the underlying design rationale,refinement tactics,experimental results from both in vitro and in vivo studies,and the translational potential into clinical practice.One focus of the discussion is the precision targeting of LNPs,particularly in the context of pulmonary genetic disorders,infectious diseases,and pulmonary malignancies.The review also addresses the existing challenges and future directions for the field,with the goal of providing a scientific foundation and strategic insights for the use of LNP-mRNA technology in pulmonary therapeutics.

关 键 词：脂质纳米颗粒 mRNA递送 肺部疾病 靶向治疗 

分 类 号：Q819[生物学—生物工程]