Development of a Library of Disulfide Bond-Containing Cationic Lipids for mRNA Delivery
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemical Reagents
2.2. Biological Reagents
2.3. Synthesis of Disulfide Lipids
2.4. Lipid Nanoparticle (LNP) Formulation
2.5. Characterization of LNPs
2.6. Cell Culture
2.7. Firefly Luciferase Activity Assay
2.8. GSH-Triggered Bioreducible Lipid Degradation
2.9. Measurement of pKa via TNS
2.10. Cell Viability
2.11. In Vivo Bioluminescent Imaging
3. Results
3.1. Design and Syntheses of Lipids
3.2. Screening of LNPs
3.3. Stability and Biological Evaluation of mRNA-LNPs
3.4. In Vivo Experiments
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Entry | Name | size (nm) | PDI | Stability | Entry | Name | Size (nm) | PDI | Stability |
---|---|---|---|---|---|---|---|---|---|
1 | C4S10 | 100 ± 23.1 | 0.266 | II | 9 | C4S18B | 62.1 ± 1.29 | 0.338 | I |
2 | C4S12 | 52.0 ± 0.49 | 0.251 | II | 10 | C4AS18A | 104 ± 1.88 | 0.131 | I |
3 | C4S14 | 102 ± 3.79 | 0.139 | II | 11 | C3S18A | 101 ± 1.41 | 0.207 | I |
4 | C4S16 | 68.1 ± 0.62 | 0.120 | II | 12 | C2S18A | 63.2 ± 0.85 | 0.323 | I |
5 | C4S18 | 122 ± 2.05 | 0.128 | II | 13 | C3AS18A | 101 ± 1.41 | 0.267 | I |
6 | C3S14 | 89.6 ± 2.84 | 0.297 | II | 14 | C3BS18A | 100 ± 1.99 | 0.183 | I |
7 | C3S16 | 110 ± 2.81 | 0.383 | II | 15 | C3CS18A | 82.8 ± 1.26 | 0.325 | I |
8 | C4S18A | 103 ± 1.03 | 0.177 | I | 16 | C3DS18A | 64.7 ± 1.08 | 0.146 | I |
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Shen, Z.; Liu, C.; Wang, Z.; Xie, F.; Liu, X.; Dong, L.; Pan, X.; Zeng, C.; Wang, P.G. Development of a Library of Disulfide Bond-Containing Cationic Lipids for mRNA Delivery. Pharmaceutics 2023, 15, 477. https://doi.org/10.3390/pharmaceutics15020477
Shen Z, Liu C, Wang Z, Xie F, Liu X, Dong L, Pan X, Zeng C, Wang PG. Development of a Library of Disulfide Bond-Containing Cationic Lipids for mRNA Delivery. Pharmaceutics. 2023; 15(2):477. https://doi.org/10.3390/pharmaceutics15020477
Chicago/Turabian StyleShen, Zhigao, Cong Liu, Ziqian Wang, Fengfei Xie, Xingwu Liu, Lingkai Dong, Xuehua Pan, Chen Zeng, and Peng George Wang. 2023. "Development of a Library of Disulfide Bond-Containing Cationic Lipids for mRNA Delivery" Pharmaceutics 15, no. 2: 477. https://doi.org/10.3390/pharmaceutics15020477
APA StyleShen, Z., Liu, C., Wang, Z., Xie, F., Liu, X., Dong, L., Pan, X., Zeng, C., & Wang, P. G. (2023). Development of a Library of Disulfide Bond-Containing Cationic Lipids for mRNA Delivery. Pharmaceutics, 15(2), 477. https://doi.org/10.3390/pharmaceutics15020477