含有可離子化陽離子脂質的膜之不穩定性：頭基排斥範圍和尾部結構的影響

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姓名

黃晧鈞(Hao-Chun Huang) 查詢紙本館藏

畢業系所

化學工程與材料工程學系

論文名稱

含有可離子化陽離子脂質的膜之不穩定性：頭基排斥範圍和尾部結構的影響
(Instability of membranes containing ionizable cationic lipids: effects of repulsive range of headgroups and tail structures)

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至系統瀏覽論文 (2028-6-30以後開放)

摘要(中)

本研究利用耗散粒子動力學來研究由可離子化陽離子脂質形成的膜之穩定性，此脂質為脂質奈米顆粒的主要成分且能夠導致內體逃逸，因此考慮了三種具有不同尾部結構的可離子化模型脂質。內體酸化導致脂質電離，造成它們頭基之間的排斥範圍增加。當靜電排斥被建模為具有遠程截止距離的保守力時，膜和囊泡會失去結構完整性並隨著截止距離超過臨界值而形成孔洞，其值隨尾部結構變化。當庫侖排斥力被明確納入和加強時，完全電離的脂質膜會失去結構完整性，顯示出與增加截止距離的保守力對膜穩定性所觀察到的定性相似的效果。隨著帶電脂質分率的增加，部分電離膜也獲得了定性相似的結果。還研究了包含可離子化脂質和典型脂質的混合脂質膜之穩定性，其雙層結構的破壞發生在足夠高的帶電分率。膜不穩定性可歸因於隨著相互作用範圍的增加，因此可以由堆疊參數的降低且顯著偏離1來解釋。

摘要(英)

The stability of membranes formed by ionizable cationic lipids, which constitute the primary components in lipid nanoparticles capable of endosomal escape, is explored using coarse-grained dissipative particle dynamics. Three types of ionizable model lipids with different tail structures are considered. Endosome acidification causes the ionization of lipids, leading to an increased repulsive range between their headgroups. When electrostatic repulsion is modeled as a conservative force with a long-range cutoff distance (r_(c,HH)), the membrane and vesicle experience a loss of structural integrity and develop holes as r_(c,HH) is beyond a critical value, which varies with the tail structure. When Coulombic repulsion is explicitly incorporated and intensified, a fully ionized lipid membrane undergoes a loss of structural integrity, displaying a qualitative similarity to the effect observed with the increase in r_(c,HH) on the membrane stability. Qualitatively similar results are obtained for partially ionized membranes as the fraction of charged lipids increases. The stability of a mixed lipid membrane containing both ionizable and conventional lipids is also investigated. The disruption of the bilayer structure occurs for sufficiently high charged fraction. The membrane instability can be attributed to the decrease in the packing parameter, which significantly deviates from unity as the interaction range increases.

關鍵字(中)

★ 脂質奈米粒
★ 可離子化陽離子脂質
★ 雙層膜
★ 遠程靜電力

關鍵字(英)

★ lipid nanoparticle
★ ionizable cationic lipid
★ bilayered membrane
★ long-range electrostatic force

論文目次

摘要 i
Abstract ii
誌謝 iii
Table of Contents iv
List of Figures v
List of Tables vi
Chapter 1 Introduction 1
Chapter 2 Model and Simulation method 4
2.1 Interactions and system parameters 4
2.2 Models of lipids 6
Chapter 3 Results and Discussion 8
3.1 Stability of membranes formed by lipids with long-range interactions 8
3.2 Impact of Coulombic interactions on ionizable cationic lipid membranes 14
3.3 Membrane instability and packing parameter 18
3.4 Rupture of stable lipid membrane by charged Lipid-D 21
Chapter 4 Conclusion 24
Reference 26

參考文獻

[1] A. J. Barbier, A. Y. Jiang, P. Zhang, R. Wooster, and D. G. Anderson, "The clinical progress of mRNA vaccines and immunotherapies," Nature biotechnology, vol. 40, no. 6, pp. 840-854, 2022.
[2] N. Chaudhary, D. Weissman, and K. A. Whitehead, "mRNA vaccines for infectious diseases: principles, delivery and clinical translation," Nature reviews Drug discovery, vol. 20, no. 11, pp. 817-838, 2021.
[3] M. L. Guevara, F. Persano, and S. Persano, "Advances in lipid nanoparticles for mRNA-based cancer immunotherapy," Frontiers in chemistry, vol. 8, p. 589959, 2020.
[4] L. Schoenmaker et al., "mRNA-lipid nanoparticle COVID-19 vaccines: Structure and stability," International journal of pharmaceutics, vol. 601, p. 120586, 2021.
[5] S. Patel et al., "Naturally-occurring cholesterol analogues in lipid nanoparticles induce polymorphic shape and enhance intracellular delivery of mRNA," Nature communications, vol. 11, no. 1, p. 983, 2020.
[6] X. Hou, T. Zaks, R. Langer, and Y. Dong, "Lipid nanoparticles for mRNA delivery," Nature Reviews Materials, vol. 6, no. 12, pp. 1078-1094, 2021.
[7] L. Xu, X. Wang, Y. Liu, G. Yang, R. J. Falconer, and C.-X. Zhao, "Lipid nanoparticles for drug delivery," Advanced NanoBiomed Research, vol. 2, no. 2, p. 2100109, 2022.
[8] T. Terada et al., "Characterization of lipid nanoparticles containing ionizable cationic lipids using design-of-experiments approach," Langmuir, vol. 37, no. 3, pp. 1120-1128, 2021.
[9] J. A. Kulkarni et al., "On the formation and morphology of lipid nanoparticles containing ionizable cationic lipids and siRNA," ACS nano, vol. 12, no. 5, pp. 4787-4795, 2018.
[10] Y. Suzuki and H. Ishihara, "Difference in the lipid nanoparticle technology employed in three approved siRNA (Patisiran) and mRNA (COVID-19 vaccine) drugs," Drug Metabolism and Pharmacokinetics, vol. 41, p. 100424, 2021.
[11] X. Huang, N. Kong, X. Zhang, Y. Cao, R. Langer, and W. Tao, "The landscape of mRNA nanomedicine," Nature Medicine, pp. 1-15, 2022.
[12] S. A. Smith, L. I. Selby, A. P. Johnston, and G. K. Such, "The endosomal escape of nanoparticles: toward more efficient cellular delivery," Bioconjugate chemistry, vol. 30, no. 2, pp. 263-272, 2018.
[13] S.-M. Chang, C. Y. Yu, and Y.-F. Chen, "Mechanism of endosomal escape by p H-responsive nucleic-acid vectors," Physical Review E, vol. 106, no. 3, p. 034408, 2022.
[14] F. Mejia, S. Khan, and B. Bilgicer, "Liposomal Targeting Modifies Endosomal Escape: Design and Mechanistic Implications," ACS Biomaterials Science & Engineering, vol. 8, no. 3, pp. 1067-1073, 2022.
[15] A. Biscans, S. Ly, N. McHugh, D. A. Cooper, and A. Khvorova, "Engineered ionizable lipid siRNA conjugates enhance endosomal escape but induce toxicity in vivo," Journal of Controlled Release, vol. 349, pp. 831-843, 2022.
[16] X. Han et al., "An ionizable lipid toolbox for RNA delivery," Nature Communications, vol. 12, no. 1, p. 7233, 2021.
[17] F. Ferraresso, A. W. Strilchuk, L. J. Juang, L. G. Poole, J. P. Luyendyk, and C. J. Kastrup, "Comparison of dlin-Mc3-Dma and alc-0315 for sirna delivery to hepatocytes and hepatic stellate cells," Molecular Pharmaceutics, vol. 19, no. 7, pp. 2175-2182, 2022.
[18] E. Kon, U. Elia, and D. Peer, "Principles for designing an optimal mRNA lipid nanoparticle vaccine," Current opinion in Biotechnology, vol. 73, pp. 329-336, 2022.
[19] P. Hoogerbrugge and J. Koelman, "Simulating microscopic hydrodynamic phenomena with dissipative particle dynamics," Europhysics letters, vol. 19, no. 3, p. 155, 1992.
[20] C.-M. Lin, C.-S. Li, Y.-J. Sheng, D. T. Wu, and H.-K. Tsao, "Size-dependent properties of small unilamellar vesicles formed by model lipids," Langmuir, vol. 28, no. 1, pp. 689-700, 2012.
[21] H.-Y. Chang, Y.-L. Lin, Y.-J. Sheng, and H.-K. Tsao, "Multilayered polymersome formed by amphiphilic asymmetric macromolecular brushes," Macromolecules, vol. 45, no. 11, pp. 4778-4789, 2012.
[22] H.-Y. Chang, H.-C. Tsai, Y.-J. Sheng, and H.-K. Tsao, "Floating and Diving Loops of ABA Triblock Copolymers in Lipid Bilayers and Stability Enhancement for Asymmetric Membranes," Biomacromolecules, vol. 22, no. 2, pp. 494-503, 2020.
[23] R. D. Groot and P. B. Warren, "Dissipative particle dynamics: Bridging the gap between atomistic and mesoscopic simulation," The Journal of chemical physics, vol. 107, no. 11, pp. 4423-4435, 1997.
[24] H. Alasiri and W. G. Chapman, "Dissipative particle dynamics (DPD) study of the interfacial tension for alkane/water systems by using COSMO-RS to calculate interaction parameters," Journal of Molecular Liquids, vol. 246, pp. 131-139, 2017.
[25] H.-L. Wu, P.-Y. Chen, C.-L. Chi, H.-K. Tsao, and Y.-J. Sheng, "Vesicle deposition on hydrophilic solid surfaces," Soft Matter, vol. 9, no. 6, pp. 1908-1919, 2013.
[26] M. Lísal, J. K. Brennan, and J. B. Avalos, "Dissipative particle dynamics at isothermal, isobaric, isoenergetic, and isoenthalpic conditions using Shardlow-like splitting algorithms," The Journal of chemical physics, vol. 135, no. 20, p. 204105, 2011.
[27] Y.-L. Yang, Y.-J. Sheng, and H.-K. Tsao, "Branching pattern effect and co-assembly with lipids of amphiphilic Janus dendrimersomes," Physical Chemistry Chemical Physics, vol. 20, no. 43, pp. 27305-27313, 2018.
[28] Y.-L. Yang, Y.-J. Sheng, and H.-K. Tsao, "Bilayered membranes of Janus dendrimers with hybrid hydrogenated and fluorinated dendrons: microstructures and coassembly with lipids," Physical Chemistry Chemical Physics, vol. 21, no. 28, pp. 15400-15407, 2019.
[29] H.-C. Tsai, Y.-L. Yang, Y.-J. Sheng, and H.-K. Tsao, "Formation of asymmetric and symmetric hybrid membranes of lipids and triblock copolymers," Polymers, vol. 12, no. 3, p. 639, 2020.
[30] Y.-C. Tseng, H.-Y. Chang, Y.-J. Sheng, and H.-K. Tsao, "Atypical vesicles and membranes with monolayer and multilayer structures formed by graft copolymers with diblock side-chains: nonlamellar structures and curvature-enhanced permeability," Soft Matter, vol. 18, no. 39, pp. 7559-7568, 2022.
[31] S. E. Feller, Y. Zhang, R. W. Pastor, and B. R. Brooks, "Constant pressure molecular dynamics simulation: The Langevin piston method," The Journal of chemical physics, vol. 103, no. 11, pp. 4613-4621, 1995.
[32] A. Maiti, J. Wescott, and P. Kung, "Nanotube–polymer composites: insights from Flory–Huggins theory and mesoscale simulations," Molecular Simulation, vol. 31, no. 2-3, pp. 143-149, 2005.
[33] Y. Eygeris, S. Patel, A. Jozic, and G. Sahay, "Deconvoluting lipid nanoparticle structure for messenger RNA delivery," Nano letters, vol. 20, no. 6, pp. 4543-4549, 2020.
[34] S. Ramachandran, S. R. Satapathy, and T. Dutta, "Delivery strategies for mRNA vaccines," Pharmaceutical medicine, vol. 36, no. 1, pp. 11-20, 2022.
[35] R. D. Groot, "Electrostatic interactions in dissipative particle dynamics—simulation of polyelectrolytes and anionic surfactants," The Journal of chemical physics, vol. 118, no. 24, pp. 11265-11277, 2003.
[36] H.-m. Ding and Y.-q. Ma, "Computer simulation of the role of protein corona in cellular delivery of nanoparticles," Biomaterials, vol. 35, no. 30, pp. 8703-8710, 2014.
[37] A. Gavrilov, A. Chertovich, and E. Y. Kramarenko, "Dissipative particle dynamics for systems with high density of charges: Implementation of electrostatic interactions," The Journal of chemical physics, vol. 145, no. 17, p. 174101, 2016.
[38] G. Gramse, A. Dols-Pérez, M. Edwards, L. Fumagalli, and G. Gomila, "Nanoscale measurement of the dielectric constant of supported lipid bilayers in aqueous solutions with electrostatic force microscopy," Biophysical journal, vol. 104, no. 6, pp. 1257-1262, 2013.
[39] J. N. Israelachvili, D. J. Mitchell, and B. W. Ninham, "Theory of self-assembly of hydrocarbon amphiphiles into micelles and bilayers," Journal of the Chemical Society, Faraday Transactions 2: Molecular and Chemical Physics, vol. 72, pp. 1525-1568, 1976.
[40] S. Liu et al., "Membrane-destabilizing ionizable phospholipids for organ-selective mRNA delivery and CRISPR–Cas gene editing," Nature materials, vol. 20, no. 5, pp. 701-710, 2021.

指導教授

曹恆光(Heng-Kwong Tsao)

審核日期

2023-6-9

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