Breaking the final barrier: Evolution of cationic and ionizable lipid structure in lipid nanoparticles to escape the endosome

IF 15.2 1区 医学 Q1 PHARMACOLOGY & PHARMACY Advanced drug delivery reviews Pub Date : 2024-09-16 DOI:10.1016/j.addr.2024.115446
{"title":"Breaking the final barrier: Evolution of cationic and ionizable lipid structure in lipid nanoparticles to escape the endosome","authors":"","doi":"10.1016/j.addr.2024.115446","DOIUrl":null,"url":null,"abstract":"<div><div>In the past decade, nucleic acid therapies have seen a boon in development and clinical translation largely due to advances in nanotechnology that have enabled their safe and targeted delivery. Nanoparticles can protect nucleic acids from degradation by serum enzymes and can facilitate entry into cells. Still, achieving endosomal escape to allow nucleic acids to enter the cytoplasm has remained a significant barrier, where less than 5% of nanoparticles within the <em>endo</em>-lysosomal pathway are able to transfer their cargo to the cytosol. Lipid-based drug delivery vehicles, particularly lipid nanoparticles (LNPs), have been optimized to achieve potent endosomal escape, and thus have been the vector of choice in the clinic as demonstrated by their utilization in the COVID-19 mRNA vaccines. The success of LNPs is in large part due to the rational design of lipids that can specifically overcome endosomal barriers. In this review, we chart the evolution of lipid structure from cationic lipids to ionizable lipids, focusing on structure–function relationships, with a focus on how they relate to endosomal escape. Additionally, we examine recent advancements in ionizable lipid structure as well as discuss the future of lipid design.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":null,"pages":null},"PeriodicalIF":15.2000,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced drug delivery reviews","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0169409X24002680","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0

Abstract

In the past decade, nucleic acid therapies have seen a boon in development and clinical translation largely due to advances in nanotechnology that have enabled their safe and targeted delivery. Nanoparticles can protect nucleic acids from degradation by serum enzymes and can facilitate entry into cells. Still, achieving endosomal escape to allow nucleic acids to enter the cytoplasm has remained a significant barrier, where less than 5% of nanoparticles within the endo-lysosomal pathway are able to transfer their cargo to the cytosol. Lipid-based drug delivery vehicles, particularly lipid nanoparticles (LNPs), have been optimized to achieve potent endosomal escape, and thus have been the vector of choice in the clinic as demonstrated by their utilization in the COVID-19 mRNA vaccines. The success of LNPs is in large part due to the rational design of lipids that can specifically overcome endosomal barriers. In this review, we chart the evolution of lipid structure from cationic lipids to ionizable lipids, focusing on structure–function relationships, with a focus on how they relate to endosomal escape. Additionally, we examine recent advancements in ionizable lipid structure as well as discuss the future of lipid design.

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
打破最后的障碍:脂质纳米颗粒中阳离子和可电离脂质结构的演变,以逃离内质体。
在过去的十年中,核酸疗法在开发和临床转化方面取得了长足的进步,这主要归功于纳米技术的进步,它使核酸的安全和靶向运输成为可能。纳米颗粒可以保护核酸不被血清酶降解,并能促进核酸进入细胞。不过,实现内溶酶体逸出以允许核酸进入细胞质仍然是一个重大障碍,只有不到 5%的内溶酶体途径颗粒能够将其货物转移到细胞质中。基于脂质的药物递送载体,尤其是脂质纳米颗粒(LNPs),已经过优化,可以实现有效的内溶酶体逃逸,因此成为临床上的首选载体,COVID-19 mRNA 疫苗中的使用就证明了这一点。LNPs 的成功在很大程度上归功于能特异性突破内体屏障的脂质的合理设计。在这篇综述中,我们描绘了从阳离子脂质到可电离脂质的脂质结构演变过程,重点介绍了结构与功能的关系,尤其是与内质体逃逸的关系。此外,我们还研究了可电离脂质结构的最新进展,并讨论了脂质设计的未来。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
CiteScore
28.10
自引率
5.00%
发文量
294
审稿时长
15.1 weeks
期刊介绍: The aim of the Journal is to provide a forum for the critical analysis of advanced drug and gene delivery systems and their applications in human and veterinary medicine. The Journal has a broad scope, covering the key issues for effective drug and gene delivery, from administration to site-specific delivery. In general, the Journal publishes review articles in a Theme Issue format. Each Theme Issue provides a comprehensive and critical examination of current and emerging research on the design and development of advanced drug and gene delivery systems and their application to experimental and clinical therapeutics. The goal is to illustrate the pivotal role of a multidisciplinary approach to modern drug delivery, encompassing the application of sound biological and physicochemical principles to the engineering of drug delivery systems to meet the therapeutic need at hand. Importantly the Editorial Team of ADDR asks that the authors effectively window the extensive volume of literature, pick the important contributions and explain their importance, produce a forward looking identification of the challenges facing the field and produce a Conclusions section with expert recommendations to address the issues.
期刊最新文献
Editorial Board Preface: RNA delivery technologies: From concept toward the clinic Delivery and kinetics of immersion optical clearing agents in tissues: Optical imaging from ex vivo to in vivo Extracellular vesicles versus lipid nanoparticles for the delivery of nucleic acids Corrigendum to “Editorial: Advanced strategies to bridge the gap between inflammation and tissue regeneration” [Adv. Drug Deliv. Rev. 209 (2024) 115328]
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1