College of Chemistry and Materials Science, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Chemical Biology Key Laboratory of HeBei University, Baoding, 071002, P. R. China.
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, No. 11, First North Road, Zhongguancun, Beijing, 100190, P. R. China.
Adv Mater. 2024 Jan;36(4):e2305300. doi: 10.1002/adma.202305300. Epub 2023 Nov 30.
Lipid nanoparticles (LNPs) are currently the most promising clinical nucleic acids drug delivery vehicles. LNPs prevent the degradation of cargo nucleic acids during blood circulation. Upon entry into the cell, specific components of the lipid nanoparticles can promote the endosomal escape of nucleic acids. These are the basic properties of lipid nanoparticles as nucleic acid carriers. As LNPs exhibit hepatic aggregation characteristics, enhancing targeting out of the liver is a crucial way to improve LNPs administrated in vivo. Meanwhile, endosomal escape of nucleic acids loaded in LNPs is often considered inadequate, and therefore, much effort is devoted to enhancing the intracellular release efficiency of nucleic acids. Here, different strategies to efficiently deliver nucleic acid delivery from LNPs are concluded and their mechanisms are investigated. In addition, based on the information on LNPs that are in clinical trials or have completed clinical trials, the issues that are necessary to be approached in the clinical translation of LNPs are discussed, which it is hoped will shed light on the development of LNP nucleic acid drugs.
脂质纳米粒（LNPs）是目前最有前途的临床核酸药物递送载体。LNPs 防止货物核酸在血液循环过程中降解。进入细胞后，脂质纳米粒的特定成分可以促进核酸的内体逃逸。这些是脂质纳米粒作为核酸载体的基本性质。由于 LNPs 表现出肝脏聚集的特性，增强肝脏以外的靶向性是提高体内给药的 LNPs 的关键途径。同时，负载在 LNPs 中的核酸的内体逃逸通常被认为是不足的，因此，人们致力于提高核酸的细胞内释放效率。本文总结了从 LNPs 中有效递送核酸的不同策略，并探讨了它们的机制。此外，基于正在临床试验或已完成临床试验的 LNPs 的信息，讨论了 LNPs 临床转化中需要解决的问题，希望这将为 LNP 核酸药物的发展提供启示。
