On the Formation and Morphology of Lipid Nanoparticles Containing Ionizable Cationic Lipids and siRNA

ACS Nano

Volumn 12, Issue 5, 2018, Pages 4787-4795

  Kulkarni, Jayesh A ^a   Darjuan, Maria M ^a   Mercer, Joanne E ^b   Chen, Sam ^a,c   Van Der Meel, Roy ^a,d   Thewalt, Jenifer L ^b   Tam, Yuen Yi C ^a,c   Cullis, Pieter R ^a  

^a UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^b SIMON FRASER UNIVERSITY   (Canada)

^c Integrated Nanotherapeutics   (Canada)

^d UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

Author keywords

cryo TEM; gene therapy; lipid biophysics; lipid nanoparticles; nanomedicine

Indexed keywords

ETHANOL; GENE THERAPY; HIGH RESOLUTION TRANSMISSION ELECTRON MICROSCOPY; LIPIDS; MEDICAL NANOTECHNOLOGY; MONOLAYERS; TRANSMISSION ELECTRON MICROSCOPY;

CRYO-TEM; CRYOGENIC TRANSMISSION ELECTRON MICROSCOPY (CRYO-TEM); DISEASE-CAUSING GENE; ELECTRON-DENSE CORE; INTRAVENOUS ADMINISTRATION; LIPID NANOPARTICLES; MECHANISM OF FORMATION; SHORT INTERFERING RNA;

NANOPARTICLES;

1,2-DISTEAROYLLECITHIN; CHOLESTEROL; LIPID; MACROGOL; NANOPARTICLE; PHOSPHATIDYLCHOLINE; SMALL INTERFERING RNA;

CHEMISTRY; GENE TRANSFER; PARTICLE SIZE; PH; PHASE TRANSITION; SURFACE PROPERTY;

CHOLESTEROL; GENE TRANSFER TECHNIQUES; HYDROGEN-ION CONCENTRATION; LIPIDS; NANOPARTICLES; PARTICLE SIZE; PHASE TRANSITION; PHOSPHATIDYLCHOLINES; POLYETHYLENE GLYCOLS; RNA, SMALL INTERFERING; SURFACE PROPERTIES;

EID: 85047643619     PISSN: 19360851     EISSN: 1936086X     Source Type: Journal    
DOI: 10.1021/acsnano.8b01516     Document Type: Article

References (25)

1. Kaczmarek, J. C.; Kowalski, P. S.; Anderson, D. G. Advances in the Delivery of Rna Therapeutics: From Concept to Clinical Reality. Genome Med. 2017, 9, 60, 10.1186/s13073-017-0450-0
2. Cullis, P. R.; Hope, M. J. Lipid Nanoparticle Systems for Enabling Gene Therapies. Mol. Ther. 2017, 25, 1467, 10.1016/j.ymthe.2017.03.013
3. Elsabahy, M.; Nazarali, A.; Foldvari, M. Non-Viral Nucleic Acid Delivery: Key Challenges and Future Directions. Curr. Drug Delivery 2011, 8, 235-44, 10.2174/156720111795256174
4. Alnylam and Sanofi Report Positive Topline Results from Apollo Phase 3 Study of Patisiran in Hereditary ATTR (hATTR) Amyloidosis Patients with Polyneuropathy. http://www.businesswire.com/news/home/20170920005628/en/, 2017, accessed Jan 11, 2018.
5. Jayaraman, M.; Ansell, S. M.; Mui, B. L.; Tam, Y. K.; Chen, J.; Du, X.; Butler, D.; Eltepu, L.; Matsuda, S.; Narayanannair, J. K.; Rajeev, K. G.; Hafez, I. M.; Akinc, A.; Maier, M. A.; Tracy, M. A.; Cullis, P. R.; Madden, T. D.; Manoharan, M.; Hope, M. J. Maximizing the Potency of siRNA Lipid Nanoparticles for Hepatic Gene Silencing in vivo. Angew. Chem., Int. Ed. 2012, 51, 8529-33, 10.1002/anie.201203263
6. Semple, S. C.; Akinc, A.; Chen, J.; Sandhu, A. P.; Mui, B. L.; Cho, C. K.; Sah, D. W.; Stebbing, D.; Crosley, E. J.; Yaworski, E.; Hafez, I. M.; Dorkin, J. R.; Qin, J.; Lam, K.; Rajeev, K. G.; Wong, K. F.; Jeffs, L. B.; Nechev, L.; Eisenhardt, M. L.; Jayaraman, M. et al. Rational Design of Cationic Lipids for siRNA Delivery. Nat. Biotechnol. 2010, 28, 172-6, 10.1038/nbt.1602
7. Belliveau, N. M.; Huft, J.; Lin, P. J.; Chen, S.; Leung, A. K.; Leaver, T. J.; Wild, A. W.; Lee, J. B.; Taylor, R. J.; Tam, Y. K.; Hansen, C. L.; Cullis, P. R. Microfluidic Synthesis of Highly Potent Limit-Size Lipid Nanoparticles for in vivo Delivery of siRNA. Mol. Ther. - Nucleic Acids 2012, 1, e37, 10.1038/mtna.2012.28
8. Leung, A. K.; Hafez, I. M.; Baoukina, S.; Belliveau, N. M.; Zhigaltsev, I. V.; Afshinmanesh, E.; Tieleman, D. P.; Hansen, C. L.; Hope, M. J.; Cullis, P. R. Lipid Nanoparticles Containing siRNA Synthesized by Microfluidic Mixing Exhibit an Electron-Dense Nanostructured Core. J. Phys. Chem. C 2012, 116, 18440-18450, 10.1021/jp303267y
9. Wan, C.; Allen, T. M.; Cullis, P. R. Lipid Nanoparticle Delivery Systems for siRNA-Based Therapeutics. Drug Delivery Transl. Res. 2014, 4, 74-83, 10.1007/s13346-013-0161-z
10. Leung, A. K.; Tam, Y. Y.; Chen, S.; Hafez, I. M.; Cullis, P. R. Microfluidic Mixing: A General Method for Encapsulating Macromolecules in Lipid Nanoparticle Systems. J. Phys. Chem. B 2015, 119, 8698-706, 10.1021/acs.jpcb.5b02891
11. Viger-Gravel, J.; Schantz, A.; Pinon, A. C.; Rossini, A. J.; Schantz, S.; Emsley, L. Structure of Lipid Nanoparticles Containing siRNA or mRNA by Dynamic Nuclear Polarization-Enhanced NMR Spectroscopy. J. Phys. Chem. B 2018, 122, 2073-2081, 10.1021/acs.jpcb.7b10795
12. Hirota, S.; de Ilarduya, C. T.; Barron, L. G.; Szoka, F. C., Jr. Simple Mixing Device to Reproducibly Prepare Cationic Lipid-DNA Complexes (Lipoplexes). Biotechniques 1999, 27, 286-90
13. Jeffs, L. B.; Palmer, L. R.; Ambegia, E. G.; Giesbrecht, C.; Ewanick, S.; MacLachlan, I. A Scalable, Extrusion-Free Method for Efficient Liposomal Encapsulation of Plasmid DNA. Pharm. Res. 2005, 22, 362-372, 10.1007/s11095-004-1873-z
14. Zhigaltsev, I. V.; Belliveau, N.; Hafez, I.; Leung, A. K.; Huft, J.; Hansen, C.; Cullis, P. R. Bottom-up Design and Synthesis of Limit Size Lipid Nanoparticle Systems with Aqueous and Triglyceride Cores Using Millisecond Microfluidic Mixing. Langmuir 2012, 28, 3633-40, 10.1021/la204833h
15. Kulkarni, J. A.; Tam, Y. Y. C.; Chen, S.; Tam, Y. K.; Zaifman, J.; Cullis, P. R.; Biswas, S. Rapid Synthesis of Lipid Nanoparticles Containing Hydrophobic Inorganic Nanoparticles. Nanoscale 2017, 9, 13600-13609, 10.1039/C7NR03272B
16. Heyes, J.; Palmer, L.; Bremner, K.; MacLachlan, I. Cationic Lipid Saturation Influences Intracellular Delivery of Encapsulated Nucleic Acids. J. Controlled Release 2005, 107, 276-87, 10.1016/j.jconrel.2005.06.014
17. Chen, S.; Tam, Y. Y. C.; Lin, P. J. C.; Sung, M. M. H.; Tam, Y. K.; Cullis, P. R. Influence of Particle Size on the in vivo Potency of Lipid Nanoparticle Formulations of siRNA. J. Controlled Release 2016, 235, 236-244, 10.1016/j.jconrel.2016.05.059
18. Hamilton, J. A.; Small, D. M. Solubilization and Localization of Triolein in Phosphatidylcholine Bilayers: A 13c Nmr Study. Proc. Natl. Acad. Sci. U. S. A. 1981, 78, 6878-82, 10.1073/pnas.78.11.6878
19. Maurer, N.; Wong, K. F.; Stark, H.; Louie, L.; McIntosh, D.; Wong, T.; Scherrer, P.; Semple, S. C.; Cullis, P. R. Spontaneous Entrapment of Polynucleotides Upon Electrostatic Interaction with Ethanol-Destabilized Cationic Liposomes. Biophys. J. 2001, 80, 2310-26, 10.1016/S0006-3495(01)76202-9
20. Semple, S. C.; Klimuk, S. K.; Harasym, T. O.; Dos Santos, N.; Ansell, S. M.; Wong, K. F.; Maurer, N.; Stark, H.; Cullis, P. R.; Hope, M. J.; Scherrer, P. Efficient Encapsulation of Antisense Oligonucleotides in Lipid Vesicles Using Ionizable Aminolipids: Formation of Novel Small Multilamellar Vesicle Structures. Biochim. Biophys. Acta, Biomembr. 2001, 1510, 152-166, 10.1016/S0005-2736(00)00343-6
21. Angelov, B.; Garamus, V. M.; Drechsler, M.; Angelova, A. Structural Analysis of Nanoparticulate Carriers for Encapsulation of Macromolecular Drugs. J. Mol. Liq. 2017, 235, 83-89, 10.1016/j.molliq.2016.11.064
22. Angelov, B.; Angelova, A.; Drechsler, M.; Garamus, V. M.; Mutafchieva, R.; Lesieur, S. Identification of Large Channels in Cationic PEGylated Cubosome Nanoparticles by Synchrotron Radiation SAXS and Cryo-Tem Imaging. Soft Matter 2015, 11, 3686-3692, 10.1039/C5SM00169B
23. Chen, S.; Tam, Y. Y.; Lin, P. J.; Leung, A. K.; Tam, Y. K.; Cullis, P. R. Development of Lipid Nanoparticle Formulations of siRNA for Hepatocyte Gene Silencing Following Subcutaneous Administration. J. Controlled Release 2014, 196, 106-12, 10.1016/j.jconrel.2014.09.025
24. Akinc, A.; Zumbuehl, A.; Goldberg, M.; Leshchiner, E. S.; Busini, V.; Hossain, N.; Bacallado, S. A.; Nguyen, D. N.; Fuller, J.; Alvarez, R.; Borodovsky, A.; Borland, T.; Constien, R.; de Fougerolles, A.; Dorkin, J. R.; Narayanannair Jayaprakash, K.; Jayaraman, M.; John, M.; Koteliansky, V.; Manoharan, M. et al. A Combinatorial Library of Lipid-Like Materials for Delivery of RNAi Therapeutics. Nat. Biotechnol. 2008, 26, 561-9, 10.1038/nbt1402
25. Basha, G.; Ordobadi, M.; Scott, W. R.; Cottle, A.; Liu, Y.; Wang, H.; Cullis, P. R. Lipid Nanoparticle Delivery of siRNA to Osteocytes Leads to Effective Silencing of Sost and Inhibition of Sclerostin in vivo. Mol. Ther. - Nucleic Acids 2016, 5, e363, 10.1038/mtna.2016.68