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阳离子脂质体2X3-DOPE的脂质组成对mRNA导入真核细胞的影响。

Influence of Lipid Composition of Cationic Liposomes 2X3-DOPE on mRNA Delivery into Eukaryotic Cells.

作者信息

Vysochinskaya Vera, Shishlyannikov Sergey, Zabrodskaya Yana, Shmendel Elena, Klotchenko Sergey, Dobrovolskaya Olga, Gavrilova Nina, Makarova Darya, Plotnikova Marina, Elpaeva Ekaterina, Gorshkov Andrey, Moshkoff Dmitry, Maslov Mikhail, Vasin Andrey

机构信息

Smorodintsev Research Institute of Influenza, 15/17 Ulitsa Professora Popova, 197376 St. Petersburg, Russia.

Institute of Biomedical Systems and Biotechnology, Peter the Great Saint Petersburg Polytechnic University, 29 Ulitsa Polytechnicheskaya, 194064 St. Petersburg, Russia.

出版信息

Pharmaceutics. 2022 Dec 20;15(1):8. doi: 10.3390/pharmaceutics15010008.

DOI:10.3390/pharmaceutics15010008
PMID:36678637
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9860636/
Abstract

The design of cationic liposomes for efficient mRNA delivery can significantly improve mRNA-based therapies. Lipoplexes based on polycationic lipid 1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetraazahexacosane tetrahydrochloride (2X3) and helper lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) were formulated in different molar ratios (1:1, 1:2, 1:3) to efficiently deliver model mRNAs to BHK-21 and A549. The objective of this study was to examine the effect of 2X3-DOPE composition as well as lipid-to-mRNA ratio (amino-to-phosphate group ratio, N/P) on mRNA transfection. We found that lipoplex-mediated transfection efficiency depends on both liposome composition and the N/P ratio. Lipoplexes with an N/P ratio of 10/1 showed nanometric hydrodynamic size, positive ζ potential, maximum loading, and transfection efficiency. Liposomes 2X3-DOPE (1:3) provided the superior delivery of both mRNA coding firefly luciferase and mRNA-eGFP into BHK-21 cells and A549 cells, compared with commercial Lipofectamine MessengerMax.

摘要

设计用于高效递送信使核糖核酸（mRNA）的阳离子脂质体可显著改善基于mRNA的疗法。基于聚阳离子脂质1,26-双（胆甾-5-烯-3β-基氧基羰基氨基）-7,11,16,20-四氮杂二十六烷四盐酸盐（2X3）和辅助脂质1,2-二油酰-sn-甘油-3-磷酸乙醇胺（DOPE）的脂质体复合物以不同摩尔比（1:1、1:2、1:3）配制，以有效地将模型mRNA递送至仓鼠肾细胞（BHK-21）和人肺癌细胞（A549）。本研究的目的是考察2X3-DOPE组成以及脂质与mRNA比例（氨基与磷酸基团比例，N/P）对mRNA转染的影响。我们发现脂质体复合物介导的转染效率取决于脂质体组成和N/P比例。N/P比例为10/1的脂质体复合物呈现纳米流体动力学尺寸、正ζ电位、最大载量和转染效率。与市售的脂质体转染试剂（Lipofectamine MessengerMax）相比，2X3-DOPE（1:3）脂质体在将编码萤火虫荧光素酶的mRNA和mRNA-eGFP递送至BHK-21细胞和A549细胞方面表现更优。

相似文献

[1]
Influence of Lipid Composition of Cationic Liposomes 2X3-DOPE on mRNA Delivery into Eukaryotic Cells.

Pharmaceutics. 2022-12-20

[2]
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[3]
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[6]
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Mol Biol (Mosk). 2017

[7]
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[8]
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[2]
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[3]
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Theranostics. 2025-1-1

[4]
Stable Polymer-Lipid Hybrid Nanoparticles Based on -Polyhydroxyalkanoate and Cationic Liposomes for mRNA Delivery.

Pharmaceutics. 2024-10-7

[5]
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Oncol Res. 2024

[6]
Brief Insights into mRNA Vaccines: Their Successful Production and Nanoformulation for Effective Response against COVID-19 and Their Potential Success for Influenza A and B.

Pathogens. 2024-6-12

[7]
Novel Efficient Lipid-Based Delivery Systems Enable a Delayed Uptake and Sustained Expression of mRNA in Human Cells and Mouse Tissues.

Pharmaceutics. 2024-5-19

[8]
Editorial for Special Issue: "Liposomal and Lipid-Based Drug Delivery Systems and Vaccines".

Pharmaceutics. 2024-2-6

[9]
Influence of the Composition of Cationic Liposomes on the Performance of Cargo Immunostimulatory RNA.

Pharmaceutics. 2023-8-23

[10]
Investigation and Comparison of Active and Passive Encapsulation Methods for Loading Proteins into Liposomes.

Int J Mol Sci. 2023-8-31

本文引用的文献

[1]
Transport of cationic liposomes in a human blood brain barrier model: Role of the stereochemistry of the gemini amphiphile on liposome biological features.

J Colloid Interface Sci. 2022-12

[2]
mRNA Lipoplexes with Cationic and Ionizable α-Amino-lipophosphonates: Membrane Fusion, Transfection, mRNA Translation and Conformation.

Pharmaceutics. 2022-3-7

[3]
Current Status and Future Perspectives on MRNA Drug Manufacturing.

Mol Pharm. 2022-4-4

[4]
Drug delivery systems for RNA therapeutics.

Nat Rev Genet. 2022-5

[5]
Principles for designing an optimal mRNA lipid nanoparticle vaccine.

Curr Opin Biotechnol. 2022-2

[6]
Challenges in the Physical Characterization of Lipid Nanoparticles.

Pharmaceutics. 2021-4-14

[7]
mRNA-lipid nanoparticle COVID-19 vaccines: Structure and stability.

Int J Pharm. 2021-5-15

[8]
Lipid-Nucleic Acid Complexes: Physicochemical Aspects and Prospects for Cancer Treatment.

Molecules. 2020-10-28

[9]
Paving the Road for RNA Therapeutics.

Trends Pharmacol Sci. 2020-10

[10]
Lipid nanoparticles for nucleic acid delivery: Current perspectives.

Adv Drug Deliv Rev. 2020

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