Development of a Library of Disulfide Bond-Containing Cationic Lipids for mRNA Delivery
Lipid nanoparticles (LNPs) are the commonly used delivery tools for messenger RNA (mRNA) therapy and play an indispensable role in the success of COVID-19 mRNA vaccines. Ionizable cationic lipids are the most important component in LNPs. Herein, we developed a series of new ionizable lipids featurin...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/2/477 |
| _version_ | 1827755915359551488 |
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| author | Zhigao Shen Cong Liu Ziqian Wang Fengfei Xie Xingwu Liu Lingkai Dong Xuehua Pan Chen Zeng Peng George Wang |
| author_facet | Zhigao Shen Cong Liu Ziqian Wang Fengfei Xie Xingwu Liu Lingkai Dong Xuehua Pan Chen Zeng Peng George Wang |
| author_sort | Zhigao Shen |
| collection | DOAJ |
| description | Lipid nanoparticles (LNPs) are the commonly used delivery tools for messenger RNA (mRNA) therapy and play an indispensable role in the success of COVID-19 mRNA vaccines. Ionizable cationic lipids are the most important component in LNPs. Herein, we developed a series of new ionizable lipids featuring bioreducible disulfide bonds, and constructed a library of lipids derived from dimercaprol. LNPs prepared from these ionizable lipids could be stored at 4 °C for a long term and are non-toxic toward HepG2 and 293T cells. In vivo experiments demonstrated that the best C4S18A formulations, which embody linoleoyl tails, show strong firefly luciferase (Fluc) mRNA expression in the liver and spleen via intravenous (IV) injection, or at the local injection site via intramuscular injection (IM). The newly designed ionizable lipids can be potentially safe and high-efficiency nanomaterials for mRNA therapy. |
| first_indexed | 2024-03-11T08:16:47Z |
| format | Article |
| id | doaj.art-51e6311a37594d8fb26682b82fc8ee35 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T08:16:47Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-51e6311a37594d8fb26682b82fc8ee352023-11-16T22:40:28ZengMDPI AGPharmaceutics1999-49232023-02-0115247710.3390/pharmaceutics15020477Development of a Library of Disulfide Bond-Containing Cationic Lipids for mRNA DeliveryZhigao Shen0Cong Liu1Ziqian Wang2Fengfei Xie3Xingwu Liu4Lingkai Dong5Xuehua Pan6Chen Zeng7Peng George Wang8Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, ChinaDepartment of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, ChinaDepartment of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, ChinaDepartment of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, ChinaDepartment of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, ChinaDepartment of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, ChinaDepartment of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, ChinaDepartment of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, ChinaDepartment of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, ChinaLipid nanoparticles (LNPs) are the commonly used delivery tools for messenger RNA (mRNA) therapy and play an indispensable role in the success of COVID-19 mRNA vaccines. Ionizable cationic lipids are the most important component in LNPs. Herein, we developed a series of new ionizable lipids featuring bioreducible disulfide bonds, and constructed a library of lipids derived from dimercaprol. LNPs prepared from these ionizable lipids could be stored at 4 °C for a long term and are non-toxic toward HepG2 and 293T cells. In vivo experiments demonstrated that the best C4S18A formulations, which embody linoleoyl tails, show strong firefly luciferase (Fluc) mRNA expression in the liver and spleen via intravenous (IV) injection, or at the local injection site via intramuscular injection (IM). The newly designed ionizable lipids can be potentially safe and high-efficiency nanomaterials for mRNA therapy.https://www.mdpi.com/1999-4923/15/2/477lipid nanoparticlesmRNA deliverydisulfide bond |
| spellingShingle | Zhigao Shen Cong Liu Ziqian Wang Fengfei Xie Xingwu Liu Lingkai Dong Xuehua Pan Chen Zeng Peng George Wang Development of a Library of Disulfide Bond-Containing Cationic Lipids for mRNA Delivery Pharmaceutics lipid nanoparticles mRNA delivery disulfide bond |
| title | Development of a Library of Disulfide Bond-Containing Cationic Lipids for mRNA Delivery |
| title_full | Development of a Library of Disulfide Bond-Containing Cationic Lipids for mRNA Delivery |
| title_fullStr | Development of a Library of Disulfide Bond-Containing Cationic Lipids for mRNA Delivery |
| title_full_unstemmed | Development of a Library of Disulfide Bond-Containing Cationic Lipids for mRNA Delivery |
| title_short | Development of a Library of Disulfide Bond-Containing Cationic Lipids for mRNA Delivery |
| title_sort | development of a library of disulfide bond containing cationic lipids for mrna delivery |
| topic | lipid nanoparticles mRNA delivery disulfide bond |
| url | https://www.mdpi.com/1999-4923/15/2/477 |
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