A microfluidic platform for the controlled synthesis of architecturally complex liquid crystalline nanoparticles.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
04 08 2023
04 08 2023
Historique:
received:
20
02
2023
accepted:
21
07
2023
medline:
7
8
2023
pubmed:
5
8
2023
entrez:
4
8
2023
Statut:
epublish
Résumé
Soft-matter nanoparticles are of great interest for their applications in biotechnology, therapeutic delivery, and in vivo imaging. Underpinning this is their biocompatibility, potential for selective targeting, attractive pharmacokinetic properties, and amenability to downstream functionalisation. Morphological diversity inherent to soft-matter particles can give rise to enhanced functionality. However, this diversity remains untapped in clinical and industrial settings, and only the simplest of particle architectures [spherical lipid vesicles and lipid/polymer nanoparticles (LNPs)] have been routinely exploited. This is partially due to a lack of appropriate methods for their synthesis. To address this, we have designed a scalable microfluidic hydrodynamic focusing (MHF) technology for the controllable, rapid, and continuous production of lyotropic liquid crystalline (LLC) nanoparticles (both cubosomes and hexosomes), colloidal dispersions of higher-order lipid assemblies with intricate internal structures of 3-D and 2-D symmetry. These particles have been proposed as the next generation of soft-matter nano-carriers, with unique fusogenic and physical properties. Crucially, unlike alternative approaches, our microfluidic method gives control over LLC size, a feature we go on to exploit in a fusogenic study with model cell membranes, where a dependency of fusion on particle diameter is evident. We believe our platform has the potential to serve as a tool for future studies involving non-lamellar soft nanoparticles, and anticipate it allowing for the rapid prototyping of LLC particles of diverse functionality, paving the way toward their eventual wide uptake at an industrial level.
Identifiants
pubmed: 37542147
doi: 10.1038/s41598-023-39205-3
pii: 10.1038/s41598-023-39205-3
pmc: PMC10403506
doi:
Substances chimiques
Polymers
0
Lipids
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
12684Informations de copyright
© 2023. Springer Nature Limited.
Références
Trantidou, T., Friddin, M. S., Salehi-Reyhani, A., Ces, O. & Elani, Y. Droplet microfluidics for the construction of compartmentalised model membranes. Lab. Chip 18(17), 2488–2509 (2018).
pubmed: 30066008
Zhao, X. et al. Microfluidic generation of nanomaterials for biomedical applications. Small 16(9), 1901943 (2020).
Lu, M. et al. Microfluidic hydrodynamic focusing for synthesis of nanomaterials. Nano Today 11(6), 778–792 (2016).
pubmed: 30337950
pmcid: 6191180
Pilkington, C. P., Seddon, J. M. & Elani, Y. Microfluidic technologies for the synthesis and manipulation of biomimetic membranous nano-assemblies. Phys. Chem. Chem. Phys. 23(6), 3693–3706 (2021).
pubmed: 33533338
Niculescu, A.-G., Chircov, C., Bîrcă, A. C. & Grumezescu, A. M. Nanomaterials synthesis through microfluidic methods: An updated overview. Nanomaterials 11(4), 864 (2021).
pubmed: 33800636
pmcid: 8066900
Alavi, M., Karimi, N. & Safaei, M. Application of various types of liposomes in drug delivery systems. Adv. Pharm. Bull. 7(1), 3–9 (2017).
pubmed: 28507932
pmcid: 5426731
Sercombe, L. et al. Advances and challenges of liposome assisted drug delivery. Front. Pharmacol. 6, 286 (2015).
pubmed: 26648870
pmcid: 4664963
Angioletti-Uberti, S. Theory, simulations and the design of functionalized nanoparticles for biomedical applications: A soft matter perspective. NPJ Comput. Mater. 3(1), 48 (2017).
Sabadasch, V., Wiehemeier, L., Kottke, T. & Hellweg, T. Core–shell microgels as thermoresponsive carriers for catalytic palladium nanoparticles. Soft Matter 16(23), 5422–5430 (2020).
pubmed: 32490485
Han, J., Liu, K., Chang, R., Zhao, L. & Yan, X. Photooxidase-mimicking nanovesicles with superior photocatalytic activity and stability based on amphiphilic amino acid and phthalocyanine co-assembly. Angew. Chem. Int. Ed. 58(7), 2000–2004 (2019).
Singh, T., Shukla, S., Kumar, P., Wahla, V. & Bajpai, V. K. Application of nanotechnology in food science: Perception and overview. Front. Microbiol. 8, 1501 (2017).
pubmed: 28824605
pmcid: 5545585
Mezzenga, R. et al. Nature-inspired design and application of lipidic lyotropic liquid crystals. Adv. Mater. 31(35), 1900818 (2019).
Gregory, A. E., Titball, R. & Williamson, D. Vaccine delivery using nanoparticles. Front. Cell. Infect. Microbiol. 3, 13–13 (2013).
pubmed: 23532930
pmcid: 3607064
Shin, M. D. et al. COVID-19 vaccine development and a potential nanomaterial path forward. Nat. Nanotechnol. 15(8), 646–655 (2020).
pubmed: 32669664
Kisby, T., Yilmazer, A. & Kostarelos, K. Reasons for success and lessons learnt from nanoscale vaccines against COVID-19. Nat. Nanotechnol. 16(8), 843–850 (2021).
pubmed: 34381200
Mitchell, M. J. et al. Engineering precision nanoparticles for drug delivery. Nat. Rev. Drug Discov. 20(2), 101–124 (2021).
pubmed: 33277608
Barriga, H. M. G., Holme, M. N. & Stevens, M. M. Cubosomes: The next generation of smart lipid nanoparticles?. Angew. Chem. Int. Ed. 58(10), 2958–2978 (2019).
Azmi, I. D., Moghimi, S. M. & Yaghmur, A. Cubosomes and hexosomes as versatile platforms for drug delivery. Ther. Deliv. 6(12), 1347–1364 (2015).
pubmed: 26652281
Dyett, B. P., Yu, H., Strachan, J., Drummond, C. J. & Conn, C. E. Fusion dynamics of cubosome nanocarriers with model cell membranes. Nat. Commun. 10(1), 4492–4492 (2019).
pubmed: 31582802
pmcid: 6776645
Dyett, B. P. et al. Uptake dynamics of cubosome nanocarriers at bacterial surfaces and the routes for cargo internalization. ACS Appl. Mater. Interfaces 13(45), 53530–53540 (2021).
pubmed: 34726885
Strachan, J. B., Dyett, B. P., Nasa, Z., Valery, C. & Conn, C. E. Toxicity and cellular uptake of lipid nanoparticles of different structure and composition. J. Colloid Interface Sci. 576, 241–251 (2020).
pubmed: 32428785
Zhang, L. et al. Theranostic combinatorial drug-loaded coated cubosomes for enhanced targeting and efficacy against cancer cells. Cell Death Dis. 11(1), 1 (2020).
pubmed: 31911576
pmcid: 6946659
Nakano, M. et al. Dispersions of liquid crystalline phases of the monoolein/oleic acid/pluronic F127 system. Langmuir 18(24), 9283–9288 (2002).
Akhlaghi, S. P., Ribeiro, I. R., Boyd, B. J. & Loh, W. Impact of preparation method and variables on the internal structure, morphology, and presence of liposomes in phytantriol-Pluronic® F127 cubosomes. Colloids Surf. B 145, 845–853 (2016).
Rahman, M. M., Byanju, B., Grewell, D. & Lamsal, B. P. High-power sonication of soy proteins: Hydroxyl radicals and their effects on protein structure. Ultrason. Sonochem. 64, 105019 (2020).
pubmed: 32078911
Daniel, R. M. & Cowan, D. A. Biomolecular stability and life at high temperatures. Cell. Mol. Life Sci. 57(2), 250–264 (2000).
pubmed: 10766021
Carugo, D., Bottaro, E., Owen, J., Stride, E. & Nastruzzi, C. Liposome production by microfluidics: potential and limiting factors. Sci. Rep. 6(1), 25876 (2016).
pubmed: 27194474
pmcid: 4872163
Yaghmur, A., Ghazal, A., Ghazal, R., Dimaki, M. & Svendsen, W. E. A hydrodynamic flow focusing microfluidic device for the continuous production of hexosomes based on docosahexaenoic acid monoglyceride. Phys. Chem. Chem. Phys. 21(24), 13005–13013 (2019).
pubmed: 31165825
Kim, D.-H. et al. A simple evaporation method for large-scale production of liquid crystalline lipid nanoparticles with various internal structures. ACS Appl. Mater. Interfaces. 7(36), 20438–20446 (2015).
pubmed: 26305487
Golden, J. P., Justin, G. A., Nasir, M. & Ligler, F. S. Hydrodynamic focusing: A versatile tool. Anal. Bioanal. Chem. 402(1), 325–335 (2012).
pubmed: 21952728
Jahn, A., Vreeland, W. N., Gaitan, M. & Locascio, L. E. Controlled vesicle self-assembly in microfluidic channels with hydrodynamic focusing. J. Am. Chem. Soc. 126(9), 2674–2675 (2004).
pubmed: 14995164
Sagalowicz, L. et al. Crystallography of dispersed liquid crystalline phases studied by cryo-transmission electron microscopy. J. Microsc. 221(2), 110–121 (2006).
pubmed: 16499550
Xu, Z., Seddon, J. M., Beales, P. A., Rappolt, M. & Tyler, A. I. I. Breaking isolation to form new networks: pH-triggered changes in connectivity inside lipid nanoparticles. J. Am. Chem. Soc. 143(40), 16556–16565 (2021).
pubmed: 34591464
Tilley, A. J., Drummond, C. J. & Boyd, B. J. Disposition and association of the steric stabilizer Pluronic® F127 in lyotropic liquid crystalline nanostructured particle dispersions. J. Colloid Interface Sci. 392, 288–296 (2013).
pubmed: 23137909
Demurtas, D. et al. Direct visualization of dispersed lipid bicontinuous cubic phases by cryo-electron tomography. Nat. Commun. 6(1), 8915 (2015).
pubmed: 26573367
Falchi, A. M. et al. Effects of monoolein-based cubosome formulations on lipid droplets and mitochondria of HeLa cells. Toxicol. Res. 4(4), 1025–1036 (2015).
Dong, Y.-D., Larson, I., Hanley, T. & Boyd, B. J. Bulk and dispersed aqueous phase behavior of phytantriol: Effect of vitamin E acetate and F127 polymer on liquid crystal nanostructure. Langmuir 22(23), 9512–9518 (2006).
pubmed: 17073473
Wang, H., Zetterlund, P. B., Boyer, C. & Spicer, P. T. Polymerization of cubosome and hexosome templates to produce complex microparticle shapes. J. Colloid Interface Sci. 546, 240–250 (2019).
pubmed: 30925432
Leforestier, A. & Livolant, F. Structure of toroidal DNA collapsed inside the phage capsid. Proc. Natl. Acad. Sci. 106(23), 9157–9162 (2009).
pubmed: 19470490
pmcid: 2695091
Tyler, A. I., Law, R. V. & Seddon, J. M. X-ray diffraction of lipid model membranes. Methods Mol. Biol. 1232, 199–225 (2015).
pubmed: 25331138
Israelachvili, J. N. Intermolecular and Surface Forces 3rd edn. (Elsevier, 2010).
Seddon, J. M. Structure of the inverted hexagonal (HII) phase, and non-lamellar phase transitions of lipids. Biochim. Biophys. Acta 1031(1), 1–69 (1990).
pubmed: 2407291
Briggs, J., Chung, H. & Caffrey, M. The temperature-composition phase diagram and mesophase structure characterization of the monoolein/water system. J. Phys. II France 6(5), 723–751 (1996).
Tyler, A. I. I. et al. Electrostatic swelling of bicontinuous cubic lipid phases. Soft Matter 11(16), 3279–3286 (2015).
pubmed: 25790335
Chang, C., Meikle, T. G., Drummond, C. J., Yang, Y. & Conn, C. E. Comparison of cubosomes and liposomes for the encapsulation and delivery of curcumin. Soft Matter 17(12), 3306–3313 (2021).
pubmed: 33623948
Deshpande, S., Caspi, Y., Meijering, A. & Dekker, C. Octanol-assisted liposome assembly on chip. Nat. Commun. 7, 10447 (2016).
pubmed: 26794442
pmcid: 4735860
Góźdź, W. T. Cubosome topologies at various particle sizes and crystallographic symmetries. Langmuir 31(49), 13321–13326 (2015).
pubmed: 26587642
Golani, G. & Schwarz, U. S. High curvature promotes fusion of lipid membranes: Predictions from continuum elastic theory. Biophys. J. 122(10), 1868–1882 (2023).
pubmed: 37077047
Hood, R. R. & DeVoe, D. L. High-throughput continuous flow production of nanoscale liposomes by microfluidic vertical flow focusing. Small 11(43), 5790–5799 (2015).
pubmed: 26395346
Friddin, M. S., Elani, Y., Trantidou, T. & Ces, O. New directions for artificial cells using prototyped biosystems.. Anal. Chem. 91(8), 4921–4928 (2019).
Luo, X., Su, P., Zhang, W. & Raston, C. L. Microfluidic devices in fabricating nano or micromaterials for biomedical applications. Adv. Mater. Technol. 4(12), 1900488 (2019).
Hood, R. R., Vreeland, W. N. & DeVoe, D. L. Microfluidic remote loading for rapid single-step liposomal drug preparation. Lab Chip 14(17), 3359–3367 (2014).
pubmed: 25003823
pmcid: 4131864
Pauw, B. R., Smith, A. J., Snow, T., Terrill, N. J. & Thunemann, A. F. The modular small-angle X-ray scattering data correction sequence. J. Appl. Crystallogr. 50(6), 1800–1811 (2017).
pubmed: 29217992
pmcid: 5713144