Microfluidics Synthesis of Gene Silencing Cubosomes

Kim, Hojun; Sung, Jaeuk; Chang, Yunju; Alfeche, Alana; Leal, Cecilia

doi:10.1021/acsnano.8b03770

Microfluidics Synthesis of Gene Silencing Cubosomes

Journal Article · Mon Aug 06 00:00:00 UTC 2018 · ACS Nano

DOI:https://doi.org/10.1021/acsnano.8b03770· OSTI ID:1478119

^[1]; Sung, Jaeuk ^[2]; Chang, Yunju ^[2]; Alfeche, Alana ^[2]; ^[2]

Univ. of Illinois at Urbana-Champaign, IL (United States); Korea Institute of Science and Technology (KIST), Seoul (Republic of Korea)
Univ. of Illinois at Urbana-Champaign, IL (United States)

The success of gene technologies hinges on our ability to engineer superior encapsulation and delivery vectors. Cubosomes are lipid-based nanoparticles where membranes, instead of enveloping into classic liposomes, intertwine into complex arrays of pores well-ordered in a cubic lattice. These complex nanoparticles encapsulate large contents of siRNA compared to a liposomal analogue. Importantly, the membranes that form cubosomes have intrinsic fusogenic properties that promote fast endosomal escape. Despite the great potential, traditional routes of forming cubosomes lead to particle sizes too large to fulfill the state-of-the art requirements of delivery vectors. To overcome this challenge, in this work we utilize a microfluidic nanomanufacturing device to synthesize cubosomes and siRNA-loaded cubosomes, termed cuboplexes. Utilizing cryogenic TEM and small angle X-ray scattering we elucidate the time-resolved mechanisms in which microfluidic devices allow the production of small cubosomes and cuboplexes (75 nm) that outperform commercially available delivery vectors, as well as liposome-based systems.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE Office of Science (SC)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1478119

Journal Information:: ACS Nano, Journal Name: ACS Nano Journal Issue: 9 Vol. 12; ISSN 1936-0851

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: ENGLISH

References (44)

Lipidic Cubic-Phase Nanoparticles-Cubosomes for Efficient Drug Delivery to Cancer Cells Nazaruk, Ewa; Majkowska-Pilip, Agnieszka; Bilewicz, Renata ChemPlusChem, Vol. 82, Issue 4 https://doi.org/10.1002/cplu.201600534	journal	January 2017
New multivalent cationic lipids reveal bell curve for transfection efficiency versus membrane charge density: lipid-DNA complexes for gene delivery Ahmad, Ayesha; Evans, Heather M.; Ewert, Kai The Journal of Gene Medicine, Vol. 7, Issue 6 https://doi.org/10.1002/jgm.717	journal	January 2005
Starvation effects on the ultrastructure of amoeba mitochondria Daniels, Edward W.; Breyer, Evelyn P. Zeitschrift f�r Zellforschung und Mikroskopische Anatomie, Vol. 91, Issue 2 https://doi.org/10.1007/BF00364307	journal	January 1968
Cubic lipid-protein-water phases Buchheim, W.; Larsson, K. Journal of Colloid and Interface Science, Vol. 117, Issue 2 https://doi.org/10.1016/0021-9797(87)90422-X	journal	June 1987
Three-Dimensional Imaging of Lipid Gene-Carriers: Membrane Charge Density Controls Universal Transfection Behavior in Lamellar Cationic Liposome-DNA Complexes Lin, Alison J.; Slack, Nelle L.; Ahmad, Ayesha Biophysical Journal, Vol. 84, Issue 5 https://doi.org/10.1016/S0006-3495(03)70055-1	journal	May 2003
Characterization and potential applications of nanostructured aqueous dispersions Yaghmur, Anan; Glatter, Otto Advances in Colloid and Interface Science, Vol. 147-148 https://doi.org/10.1016/j.cis.2008.07.007	journal	March 2009
Progress in liquid crystalline dispersions: Cubosomes Spicer, Patrick T. Current Opinion in Colloid & Interface Science, Vol. 10, Issue 5-6 https://doi.org/10.1016/j.cocis.2005.09.004	journal	December 2005
Single-step microfluidic synthesis of transferrin-conjugated lipid nanoparticles for siRNA delivery Li, Yujing; Lee, Robert J.; Huang, Xueqin Nanomedicine: Nanotechnology, Biology and Medicine, Vol. 13, Issue 2 https://doi.org/10.1016/j.nano.2016.09.014	journal	February 2017
Do viruses subvert cholesterol homeostasis to induce host cubic membranes? Deng, Yuru; Almsherqi, Zakaria A.; Ng, Mary M. L. Trends in Cell Biology, Vol. 20, Issue 7 https://doi.org/10.1016/j.tcb.2010.04.001	journal	July 2010
Influence of Cubosome Surface Architecture on Its Cellular Uptake Mechanism Deshpande, Sonal; Singh, Neetu Langmuir, Vol. 33, Issue 14 https://doi.org/10.1021/acs.langmuir.6b04423	journal	March 2017
A Simple Evaporation Method for Large-Scale Production of Liquid Crystalline Lipid Nanoparticles with Various Internal Structures Kim, Do-Hoon; Lim, Sora; Shim, Jongwon ACS Applied Materials & Interfaces, Vol. 7, Issue 36 https://doi.org/10.1021/acsami.5b06413	journal	August 2015
Why Do Membranes of Some Unhealthy Cells Adopt a Cubic Architecture? Xiao, Qi; Wang, Zhichun; Williams, Dewight ACS Central Science, Vol. 2, Issue 12 https://doi.org/10.1021/acscentsci.6b00284	journal	November 2016
Cuboplexes: Topologically Active siRNA Delivery Kim, Hojun; Leal, Cecilia ACS Nano, Vol. 9, Issue 10 https://doi.org/10.1021/acsnano.5b03902	journal	September 2015
Structure and Gene Silencing Activities of Monovalent and Pentavalent Cationic Lipid Vectors Complexed with siRNA ^† Bouxsein, Nathan F.; McAllister, Christopher S.; Ewert, Kai K. Biochemistry, Vol. 46, Issue 16 https://doi.org/10.1021/bi062138l	journal	April 2007
Cubic lipid-water phases: structures and biomembrane aspects Larsson, K. The Journal of Physical Chemistry, Vol. 93, Issue 21 https://doi.org/10.1021/j100358a010	journal	October 1989
Highly Efficient Gene Silencing Activity of siRNA Embedded in a Nanostructured Gyroid Cubic Lipid Matrix Leal, Cecília; Bouxsein, Nathan F.; Ewert, Kai K. Journal of the American Chemical Society, Vol. 132, Issue 47 https://doi.org/10.1021/ja1059763	journal	December 2010
Novel Process for Producing Cubic Liquid Crystalline Nanoparticles (Cubosomes) Spicer, Patrick T.; Hayden, Kristin L.; Lynch, Matthew L. Langmuir, Vol. 17, Issue 19 https://doi.org/10.1021/la010161w	journal	September 2001
“Sponge” Nanoparticle Dispersions in Aqueous Mixtures of Diglycerol Monooleate, Glycerol Dioleate, and Polysorbate 80 Barauskas, Justas; Misiunas, Audrius; Gunnarsson, Torsten Langmuir, Vol. 22, Issue 14 https://doi.org/10.1021/la060295f	journal	July 2006
Dispersed Lipid Liquid Crystalline Phases Stabilized by a Hydrophobically Modified Cellulose Almgren, Mats; Borné, Johanna; Feitosa, Eloi Langmuir, Vol. 23, Issue 5 https://doi.org/10.1021/la062482j	journal	February 2007
Revisiting β-Casein as a Stabilizer for Lipid Liquid Crystalline Nanostructured Particles Zhai, Jiali; Waddington, Lynne; Wooster, Tim J. Langmuir, Vol. 27, Issue 24 https://doi.org/10.1021/la203061f	journal	December 2011
Internally Self-Assembled Submicrometer Emulsions Stabilized with a Charged Polymer or with Silica Particles Dulle, Martin; Glatter, Otto Langmuir, Vol. 28, Issue 2 https://doi.org/10.1021/la203880a	journal	December 2011
High-Throughput Discovery of Novel Steric Stabilizers for Cubic Lyotropic Liquid Crystal Nanoparticle Dispersions Chong, Josephine Y. T.; Mulet, Xavier; Waddington, Lynne J. Langmuir, Vol. 28, Issue 25 https://doi.org/10.1021/la301874v	journal	June 2012
Single Crystallization of an Inverse Bicontinuous Cubic Phase of a Lipid Oka, Toshihiko; Hojo, Hiroki Langmuir, Vol. 30, Issue 28 https://doi.org/10.1021/la502002r	journal	July 2014
Facile Dispersion and Control of Internal Structure in Lyotropic Liquid Crystalline Particles by Auxiliary Solvent Evaporation Martiel, Isabelle; Sagalowicz, Laurent; Handschin, Stephan Langmuir, Vol. 30, Issue 48 https://doi.org/10.1021/la5038662	journal	November 2014
Self-Assembled Lipid Superstructures: Beyond Vesicles and Liposomes Barauskas, Justas; Johnsson, Markus; Tiberg, Fredrik Nano Letters, Vol. 5, Issue 8 https://doi.org/10.1021/nl050678i	journal	August 2005
Impact of Nanotechnology on Drug Delivery Farokhzad, Omid C.; Langer, Robert ACS Nano, Vol. 3, Issue 1 https://doi.org/10.1021/nn900002m	journal	December 2008
Two cubic phases in monoolein–water system Larsson, K. Nature, Vol. 304, Issue 5927 https://doi.org/10.1038/304664c0	journal	August 1983
Microfluidic Synthesis of Highly Potent Limit-size Lipid Nanoparticles for In Vivo Delivery of siRNA Belliveau, Nathan M.; Huft, Jens; Lin, Paulo JC Molecular Therapy - Nucleic Acids, Vol. 1 https://doi.org/10.1038/mtna.2012.28	journal	January 2012
Lipid Nanoparticle Delivery of siRNA to Silence Neuronal Gene Expression in the Brain Rungta, Ravi L.; Choi, Hyun B.; Lin, Paulo JC Molecular Therapy—Nucleic Acids, Vol. 2, Issue 11 https://doi.org/10.1038/mtna.2013.65	journal	December 2013
Lipid nanoparticle siRNA treatment of Ebola-virus-Makona-infected nonhuman primates Thi, Emily P.; Mire, Chad E.; Lee, Amy C. H. Nature, Vol. 521, Issue 7552 https://doi.org/10.1038/nature14442	journal	April 2015
Efficiency of siRNA delivery by lipid nanoparticles is limited by endocytic recycling Sahay, Gaurav; Querbes, William; Alabi, Christopher Nature Biotechnology, Vol. 31, Issue 7 https://doi.org/10.1038/nbt.2614	journal	June 2013
Biodegradable silicon nanoneedles delivering nucleic acids intracellularly induce localized in vivo neovascularization Chiappini, C.; De Rosa, E.; Martinez, J. O. Nature Materials, Vol. 14, Issue 5 https://doi.org/10.1038/nmat4249	journal	March 2015
Soft drug delivery systems Malmsten, Martin Soft Matter, Vol. 2, Issue 9 https://doi.org/10.1039/b608348j	journal	January 2006
Steric stabilisation of self-assembled cubic lyotropic liquid crystalline nanoparticles: high throughput evaluation of triblock polyethylene oxide-polypropylene oxide-polyethylene oxide copolymers Chong, Josephine Y. T.; Mulet, Xavier; Waddington, Lynne J. Soft Matter, Vol. 7, Issue 10 https://doi.org/10.1039/c1sm05181d	journal	January 2011
Hemophilia B Gene Therapy with a High-Specific-Activity Factor IX Variant George, Lindsey A.; Sullivan, Spencer K.; Giermasz, Adam New England Journal of Medicine, Vol. 377, Issue 23 https://doi.org/10.1056/NEJMoa1708538	journal	December 2017
Self-assembled lamellar complexes of siRNA with lipidic aminoglycoside derivatives promote efficient siRNA delivery and interference Desigaux, L.; Sainlos, M.; Lambert, O. Proceedings of the National Academy of Sciences, Vol. 104, Issue 42 https://doi.org/10.1073/pnas.0707431104	journal	October 2007
Investigating the optimal size of anticancer nanomedicine Tang, L.; Yang, X.; Yin, Q. Proceedings of the National Academy of Sciences, Vol. 111, Issue 43 https://doi.org/10.1073/pnas.1411499111	journal	October 2014
Super-swelled lyotropic single crystals Kim, Hojun; Song, Ziyuan; Leal, Cecilia Proceedings of the National Academy of Sciences, Vol. 114, Issue 41 https://doi.org/10.1073/pnas.1710774114	journal	September 2017
Cubic membranes: a legend beyond the Flatland* of cell membrane organization Almsherqi, Zakaria A.; Kohlwein, Sepp D.; Deng, Yuru The Journal of Cell Biology, Vol. 173, Issue 6 https://doi.org/10.1083/jcb.200603055	journal	June 2006
Chaotic Mixer for Microchannels Stroock, A. D. Science, Vol. 295, Issue 5555 https://doi.org/10.1126/science.1066238	journal	January 2002
Watching fat digestion Patton, J.; Carey, M. Science, Vol. 204, Issue 4389 https://doi.org/10.1126/science.432636	journal	April 1979
Cubosomes: An Overview Garg, Gopal; Saraf, Shailendra; Saraf, Swarnlata Biological & Pharmaceutical Bulletin, Vol. 30, Issue 2 https://doi.org/10.1248/bpb.30.350	journal	January 2007
Cubosome nanoparticles potentiate immune properties of immunostimulants Wang, Deyun; Luo, Li; Zheng, Sisi International Journal of Nanomedicine, Vol. Volume 11 https://doi.org/10.2147/IJN.S110406	journal	January 2016
Nanostructed Cubosomes as Advanced Drug Delivery System Pan, Xin; Han, Ke; Peng, Xinsheng Current Pharmaceutical Design, Vol. 19, Issue 35 https://doi.org/10.2174/1381612811319350006	journal	September 2013

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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
bicontinuous cubic
cuboplexes
cubosomes
lipids
microfluidics
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Microfluidics Synthesis of Gene Silencing Cubosomes

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References (44)

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Figures / Tables (6)

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