综述
ENGLISH ABSTRACT
脂质纳米颗粒用于mRNA疫苗递送系统的研究进展
王红玉
彭沁桦
李玉华
曹守春
作者及单位信息
·
DOI: 10.3760/cma.j.cn311962-20240428-00020
Research progress of lipid nanoparticles for mRNA vaccine delivery systems
Wang Hongyu
Peng Qinhua
Li Yuhua
Cao Shouchun
Authors Info & Affiliations
Wang Hongyu
Department of Arbovirus Vaccine,National Institutes for Food and Drug Control,Beijing 102926,China
Peng Qinhua
Department of Arbovirus Vaccine,National Institutes for Food and Drug Control,Beijing 102926,China
Li Yuhua
Department of Arbovirus Vaccine,National Institutes for Food and Drug Control,Beijing 102926,China
Cao Shouchun
Department of Arbovirus Vaccine,National Institutes for Food and Drug Control,Beijing 102926,China
·
DOI: 10.3760/cma.j.cn311962-20240428-00020
0
0
0
0
0
0
PDF下载
APP内阅读
摘要

脂质纳米颗粒是由1个或多个磷脂双分子层组成的球形囊泡结构,是目前临床研究和应用中最有效的非病毒递送载体,主要用于化学药物和核酸分子的递送。2019年新型冠状病毒感染暴发后,mRNA疫苗凭借其设计与制造的简便性、低免疫原性、快速量产等优点脱颖而出。研究表明,脂质纳米颗粒作为新型冠状病毒mRNA 疫苗的重要组成部分,对其有效性和稳定性有着重要作用。此文综述目前应用较多的脂质纳米颗粒的结构、特性、应用及质量控制等方面的相关研究,以期增加对mRNA疫苗递送系统的认识,从而进一步促进mRNA疫苗和药物的快速发展。

脂质体;基因递送;脂质纳米颗粒;mRNA疫苗
ABSTRACT

Lipid nanoparticles (LNPs), with spherical vesicle structure composed of one or multiple phospholipid bilayers, are currently the most effective non-viral delivery vehicle in clinical research and application, mainly for the delivery of chemical drugs and nucleic acid molecules. Since the outbreak of COVID-19, mRNA vaccines standed out due to their simplicity of design and manufacture, low immunogenicity, and rapid large-scale production. As an important component, LNPs play an important role in the effectiveness and stability of mRNA vaccines against COVID-19. In this review, the structure, characteristics, application and quality control of the widely used LNPs are summarized, in order to provide a deeper and broader understanding to mRNA vaccine delivery systems and further promote the rapid development of mRNA vaccines and drugs.

Liposomes;Gene delivery;Lipid nanoparticle;mRNA vaccine
Cao Shouchun, Email: nc.defgrabo.cdfincsoac
引用本文

王红玉,彭沁桦,李玉华,等. 脂质纳米颗粒用于mRNA疫苗递送系统的研究进展[J]. 国际生物制品学杂志,2025,48(01):60-66.

DOI:10.3760/cma.j.cn311962-20240428-00020

PERMISSIONS

Request permissions for this article from CCC.

评价本文
*以上评分为匿名评价
脂质纳米颗粒(lipid nanoparticle,LNP)是由多种脂质成分组成的封闭微球,其结构类似生物膜,通常由阳离子脂质、胆固醇、中性脂质以及聚乙二醇(polyethylene glycol,PEG)衍生物PEG-脂质组成 1。LNP作为用途极为广泛的纳米载体平台,可以运输疏水性或亲水性分子,包括小分子、蛋白质和核酸等。1995年,首款由LNP递送的小分子药物Doxil获得FDA批准上市 2。Doxil的获批是脂质体药物递送系统的重要里程碑。2018年,LNP-小干扰RNA药物Onpattro获FDA批准上市 3,证实了LNP递送系统的有效性和安全性,巩固了LNP在药物递送领域的地位。2021年,2款新型冠状病毒mRNA疫苗BNT162b2和mRNA-1273获批上市,使LNP成为了目前研究最热门、临床应用最广泛的 mRNA 疫苗递送系统。该递送系统不但解决了mRNA不易通过细胞膜以及在体内易被核酸酶降解的问题,而且对mRNA疫苗发挥稳定性和有效性也起到了关键作用 4 , 5 , 6
试读结束,您可以通过登录机构账户或个人账户后获取全文阅读权限。
参考文献
[1]
张体鹏决利利. 白屈菜红碱2种脂质体的制备和口服生物利用度比较[J]. 中草药 20235417):5568-5579. DOI: 10.7501/j.issn.0253-2670.2023.17.011 .
返回引文位置Google Scholar
百度学术
万方数据
[2]
Gabizon AA . Pegylated liposomal doxorubicin:metamorphosis of an old drug into a new form of chemotherapy[J]. Cancer Invest 2001194):424-436. DOI: 10.1081/cnv-100103136 .
返回引文位置Google Scholar
百度学术
万方数据
[3]
Hoy SM . Patisiran:first global approval[J]. Drugs 20187815):1625-1631. DOI: 10.1007/s40265-018-0983-6 .
返回引文位置Google Scholar
百度学术
万方数据
[4]
Kubiatowicz LJ Mohapatra A Krishnan N et al. mRNA nanomedicine:design and recent applications[J]. Exploration(Beijing) 202226):20210217. DOI: 10.1002/EXP.20210217 .
返回引文位置Google Scholar
百度学术
万方数据
[5]
Akinc A Querbes W De S et al. Targeted delivery of RNAi therapeutics with endogenous and exogenous ligand-based mechanisms[J]. Mol Ther 2010187):1357-1364. DOI: 10.1038/mt.2010.85 .
返回引文位置Google Scholar
百度学术
万方数据
[6]
Najafi-Hajivar S Zakeri-Milani P Mohammadi H et al. Overview on experimental models of interactions between nanoparticles and the immune system[J]. Biomed Pharmacother 2016831365-1378. DOI: 10.1016/j.biopha.2016.08.060 .
返回引文位置Google Scholar
百度学术
万方数据
[7]
Lombardo D Calandra P Barreca D et al. Soft interaction in liposome nanocarriers for therapeutic drug delivery[J]. Nanomaterials(Basel) 201667):125. DOI: 10.3390/nano6070125 .
返回引文位置Google Scholar
百度学术
万方数据
[8]
Hoyer J Neundorf I . Peptide vectors for the nonviral delivery of nucleic acids[J]. Acc Chem Res 2012457):1048-1056. DOI: 10.1021/ar2002304 .
返回引文位置Google Scholar
百度学术
万方数据
[9]
<x>Sama</x> <x>ridou</x> E Heyes J Lutwyche P . Lipid nanoparticles for nucleic acid delivery:current perspectives[J]. Adv Drug Deliv Rev 2020154/15537-63. DOI: 10.1016/j.addr.2020.06.002 .
返回引文位置Google Scholar
百度学术
万方数据
[10]
Semple SC Akin A Chen J et al. Rational design of cationic lipids for siRNA delivery[J]. Nat Biotechnol 2010282):172-176. DOI: 10.1038/nbt.1602 .
返回引文位置Google Scholar
百度学术
万方数据
[11]
Choi JS Lee EJ Jang HS et al. New cationic liposomes for gene transfer into mammalian c ells with high efficiency and low toxicity [J]. Bioconjug Chem 2001121):108-113. DOI: 10.1021/bc000081o .
返回引文位置Google Scholar
百度学术
万方数据
[12]
Koynova R Wang L MacDonald RC . Cationic phospholipids forming cubic phases:lipoplex structure and transfection efficiency[J]. Mol Pharm 200855):739-744. DOI: 10.1021/mp800011e .
返回引文位置Google Scholar
百度学术
万方数据
[13]
Li L Song H Luo K et al. Gene transfer efficacies of serum-resistant amino acids-based cationic lipids:dependence on headgroup,lipoplex stability and cellular uptake[J]. Int J Pharm 20114081/2):183-190. DOI: 10.1016/j.ijpharm.2011.01.051 .
返回引文位置Google Scholar
百度学术
万方数据
[14]
Kawakami S Yamashita F Nishikawa M et al. Asialoglycoprotein receptor-mediated gene transfer using novel galactosylated cationic liposomes[J]. Biochem Biophys Res Commun 19982521):78-83. DOI: 10.1006/bbrc.1998.9602 .
返回引文位置Google Scholar
百度学术
万方数据
[15]
Allen TM Cullis PR . Liposomal drug delivery systems:from concept to clinical applications[J]. Adv Drug Deliv Rev 2013651):36-48. DOI: 10.1016/j.addr.2012.09.037 .
返回引文位置Google Scholar
百度学术
万方数据
[16]
Chen Q Xu S Liu S et al. Emerging nanomedicines of paclitaxel for cancer treatment[J]. J Control Release 2022342280-294. DOI: 10.1016/j.jconrel.2022.01.010 .
返回引文位置Google Scholar
百度学术
万方数据
[17]
Eichhorn ME Luedemann S Strieth S et al. Cationic lipid complexed camptothecin(EndoTAG-2)improves antitumoral efficacy by tumor vascular targeting[J]. Cancer Biol Ther 200766):920-929. DOI: 10.4161/cbt.6.6.4207 .
返回引文位置Google Scholar
百度学术
万方数据
[18]
Hald Albertsen C Kulkarni JA Witzigmann D et al. The role of lipid components in lipid nanoparticles for vaccines and gene therapy[J]. Adv Drug Deliv Rev 2022188114416. DOI: 10.1016/j.addr.2022.114416 .
返回引文位置Google Scholar
百度学术
万方数据
[19]
Zhang L More KR Ojha A et al. Effect of mRNA-LNP components of two globally-marketed COVID-19 vaccines on efficacy and stability[J]. NPJ Vaccines 202381):156. DOI: 10.1038/s41541-023-00751-6 .
返回引文位置Google Scholar
百度学术
万方数据
[20]
Kiaie SH Majidi Zolbanin N Ahmadi A et al. Recent advances in mRNA-LNP therapeutics:immunological and pharmacological aspects[J]. J Nanobiotechnology 2022201):276. DOI: 10.1186/s12951-022-01478-7 .
返回引文位置Google Scholar
百度学术
万方数据
[21]
Fang E Liu X Li M et al. Advances in COVID-19 mRNA vaccine development[J]. Signal Transduct Target Ther 202271):94. DOI: 10.1038/s41392-022-00950-y .
返回引文位置Google Scholar
百度学术
万方数据
[22]
Hashizaki K Taguchi H Itoh C et al. Effects of poly(ethylene glycol)(PEG)concentration on the permeability of PEG-grafted liposomes[J]. Chem Pharm Bull(Tokyo) 2005531):27-31. DOI: 10.1248/cpb.53.27 .
返回引文位置Google Scholar
百度学术
万方数据
[23]
Hashizaki K Taguchi H Itoh C et al. Effects of poly(ethylene glycol)(PEG)chain length of PEG-lipid on the permeability of liposomal bilayer membranes[J]. Chem Pharm Bull(Tokyo) 2003517):815-820. DOI: 10.1248/cpb.51.815 .
返回引文位置Google Scholar
百度学术
万方数据
[24]
Chaudhary N Weissman D Whitehead KA . mRNA vaccines for infectious diseases:principles,delivery and clinical translation[J]. Nat Rev Drug Discov 20212011):817-838. DOI: 10.1038/s41573-021-00283-5 .
返回引文位置Google Scholar
百度学术
万方数据
[25]
Semple SC Klimuk SK Harasym TO . Efficient encapsulation of antisense oligonucleotides in lipid vesicles using ionizable aminolipids:formation of novel small multilamellar vesicle structures[J]. Biochim Biophys Acta 200115101/2):152-166. DOI: 10.1016/s0005-2736(00)00343-6 .
返回引文位置Google Scholar
百度学术
万方数据
[26]
Song LY Ahkong QF Rong Q et al. Characterization of the inhibitory effect of PEG-lipid conjugates on the intracellular delivery of plasmid and antisense DNA mediated by cationic lipid liposomes[J]. Biochim Biophysica Acta 200215581):1-13. DOI: 10.1016/s0005-2736(01)00399-6 .
返回引文位置Google Scholar
百度学术
万方数据
[27]
Yeagle PL . Modulation of membrane function by cholesterol[J]. Biochimie 199173):10-1303. 1310DOI: 10.1016/0300-9084(91)90093-g .
返回引文位置Google Scholar
百度学术
万方数据
[28]
Paunovska K Da Silva Sanchez AJ Sago CD et al. Nanoparticles containing oxidized cholesterol deliver mRNA to the liver microenvironment at clinically relevant doses[J]. Adv Mater 20193114):e1807748. DOI: 10.1002/adma.201807748 .
返回引文位置Google Scholar
百度学术
万方数据
[29]
Wang C Siriwardane DA Jiang W et al. Quantitative analysis of cholesterol oxidation products and desmosterol in parenteral liposomal pharmaceutical formulations[J]. Int J Pharm 2019569118576. DOI: 10.1016/j.ijpharm.2019.118576 .
返回引文位置Google Scholar
百度学术
万方数据
[30]
Paunovska K Gil CJ Lokugamage MP et al. Analyzing 2000 in vivo drug delivery data points reveals cholesterol structure impacts nanoparticle delivery [J]. ACS Nano 2018128):8341-8349. DOI: 10.1021/acsnano.8b03640 .
返回引文位置Google Scholar
百度学术
万方数据
[31]
Cheng X Lee RJ . The role of helper lipids in lipid nanoparticles(LNPs)designed for oligonucleotide delivery[J]. Adv Drug Deliv Rev 201699Pt A):129-137. DOI: 10.1016/j.addr.2016.01.022 .
返回引文位置Google Scholar
百度学术
万方数据
[32]
Cheng Q Wei T Farbiak L et al. Selective organ targeting(SORT)nanoparticles for tissue-specific mRNA delivery and CRISPR-Cas gene editing[J]. Nat Nanotechnol 2020154):313-320. DOI: 10.1038/s41565-020-0669-6 .
返回引文位置Google Scholar
百度学术
万方数据
[33]
Torchilin V Weisslg V . Liposomes:a practical approach[M/OL]. OxfordOxford University Press 20032024-01-25]. https://academic.oup.com/book/53573.
[34]
Zhang H . Thin-film hydration followed by extrusion method for liposome preparation[J]. Methods Mol Biol 2023262257-63. DOI: 10.1007/978-1-0716-2954-3_4 .
返回引文位置Google Scholar
百度学术
万方数据
[35]
Lepeltier E Bourgaux C Couvreur P . Nanoprecipitation and the "Ouzo effect":application to drug delivery devices[J]. Adv Drug Deliv Rev 20147186-97. DOI: 10.1016/j.addr.2013.12.009 .
返回引文位置Google Scholar
百度学术
万方数据
[36]
Akinc A Maier MA Manoharan M et al. The Onpattro story and the clinical translation of nanomedicines containing nucleic acid-based drugs[J]. Nat Nanotechnol 20191412):1084-1087. DOI: 10.1038/s41565-019-0591-y .
返回引文位置Google Scholar
百度学术
万方数据
[37]
KNAUER Gmbh. 使用KNAUER IJM NanoScaler设备进行LNP配方的开发和优化[EB/OL].( 2022-11-07)[2024-01-25]. http://www.knauer.net.cn/index.php?r=site%2Fnews-detail & nid=31 .
返回引文位置Google Scholar
百度学术
万方数据
[38]
Kon E Elia U Peer D . Principles for designing an optimal mRNA lipid nanoparticle vaccine[J]. Curr Opin Biotechnol 202273329-336. DOI: 10.1016/j.copbio.2021.09.016 .
返回引文位置Google Scholar
百度学术
万方数据
[39]
Zhang W Pfeifle A Lansdell C et al. The expression kinetics and immunogenicity of lipid nanoparticles delivering plasmid DNA and mRNA in mice[J]. Vaccines(Basel) 20231110):1580. DOI: 10.3390/vaccines11101580 .
返回引文位置Google Scholar
百度学术
万方数据
[40]
Escalona-Rayo O Zeng Y Knol RA et al. In vitro and in vivo evaluation of clinically-approved ionizable cationic lipids shows divergent results between mRNA transfection and vaccine efficacy [J]. Biomed Pharmacother 2023165115065. DOI: 10.1016/j.biopha.2023.115065 .
返回引文位置Google Scholar
百度学术
万方数据
[41]
Schoenmaker L Witzigmann D Kulkarni JA et al. mRNA-lipid nanoparticle COVID-19 vaccines:structure and stability[J]. Int J Pharm 2021601120586. DOI: 10.1016/j.ijpharm.2021.120586 .
返回引文位置Google Scholar
百度学术
万方数据
[42]
Teo SP . Review of COVID-19 mRNA vaccines:BNT162b2 and mRNA-1273[J]. J Pharm Pract 2022356):947-951. DOI: 10.1177/08971900211009650 .
返回引文位置Google Scholar
百度学术
万方数据
[43]
Cui S Wang Y Gong Y et al. Correlation of the cytotoxic effects of cationic lipids with their headgroups[J]. Toxicol Res(Camb) 201873):473-479. DOI: 10.1039/c8tx00005k .
返回引文位置Google Scholar
百度学术
万方数据
[44]
Hassett KJ Higgins J Woods A et al. Impact of lipid nanoparticle size on mRNA vaccine immunogenicity[J]. J Control Release 2021335237-246. DOI: 10.1016/j.jconrel.2021.05.021 .
返回引文位置Google Scholar
百度学术
万方数据
[45]
刘歆徐根明郭江峰. 基于SYBR Green Ⅰ的双链DNA定量方法[J]. 中国生物工程杂志 2008281):55-60. DOI: 10.13523/j.cb.20080110 .
返回引文位置Google Scholar
百度学术
万方数据
[46]
Patel P Ibrahim NM Cheng K . The importance of apparent pKa in the development of nanoparticles encapsulating siRNA and mRNA[J]. Trends Pharmacol Sci 2021426):448-460. DOI: 10.1016/j.tips.2021.03.002 .
返回引文位置Google Scholar
百度学术
万方数据
[47]
佟乐孙巍杨亚莉. mRNA脂质纳米颗粒生产质量控制关键考虑要点分析及探究[J]. 中国食品药品监管 202212):16-23. DOI: 10.3969/j.issn.1673-5390.2022.12.002 .
返回引文位置Google Scholar
百度学术
万方数据
备注信息
A
曹守春,Email: nc.defgrabo.cdfincsoac
B
所有作者均声明不存在利益冲突
评论 (0条)
注册
登录
时间排序
暂无评论,发表第一条评论抢沙发
MedAI助手(体验版)
文档即答
智问智答
机器翻译
回答内容由人工智能生成,我社无法保证其准确性和完整性,该生成内容不代表我们的态度或观点,仅供参考。
生成快照
文献快照

你好,我可以帮助您更好的了解本文,请向我提问您关注的问题。

0/2000

《中华医学会杂志社用户协议》 | 《隐私政策》

《SparkDesk 用户协议》 | 《SparkDesk 隐私政策》

网信算备340104764864601230055号 | 网信算备340104726288401230013号

技术支持:

历史对话
本文全部
还没有聊天记录
设置
模式
纯净模式沉浸模式
字号