Size-Selective Transfer of Lipid Nanoparticle-Based Drug Carriers Across the Blood Brain Barrier Via Vascular Occlusions Following Traumatic Brain Injury.
blood-brain barrier
brain injury
correlative light-electron microscopy
drug delivery
nanoparticles
Journal
Small (Weinheim an der Bergstrasse, Germany)
ISSN: 1613-6829
Titre abrégé: Small
Pays: Germany
ID NLM: 101235338
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
revised:
10
03
2022
received:
15
01
2022
pubmed:
7
4
2022
medline:
7
5
2022
entrez:
6
4
2022
Statut:
ppublish
Résumé
The current lack of understanding about how nanocarriers cross the blood-brain barrier (BBB) in the healthy and injured brain is hindering the clinical translation of nanoscale brain-targeted drug-delivery systems. Here, the bio-distribution of lipid nano-emulsion droplets (LNDs) of two sizes (30 and 80 nm) in the mouse brain after traumatic brain injury (TBI) is investigated. The highly fluorescent LNDs are prepared by loading them with octadecyl rhodamine B and a bulky hydrophobic counter-ion, tetraphenylborate. Using in vivo two-photon and confocal imaging, the circulation kinetics and bio-distribution of LNDs in the healthy and injured mouse brain are studied. It is found that after TBI, LNDs of both sizes accumulate at vascular occlusions, where specifically 30 nm LNDs extravasate into the brain parenchyma and reach neurons. The vascular occlusions are not associated with bleedings, but instead are surrounded by processes of activated microglia, suggesting a specific opening of the BBB. Finally, correlative light-electron microscopy reveals 30 nm LNDs in endothelial vesicles, while 80 nm particles remain in the vessel lumen, indicating size-selective vesicular transport across the BBB via vascular occlusions. The data suggest that microvascular occlusions serve as "gates" for the transport of nanocarriers across the BBB.
Identifiants
pubmed: 35384294
doi: 10.1002/smll.202200302
doi:
Substances chimiques
Drug Carriers
0
Lipid Nanoparticles
0
Liposomes
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2200302Subventions
Organisme : European Research Council
ID : 648528
Pays : International
Organisme : Marie Curie
Pays : United Kingdom
Informations de copyright
© 2022 The Authors. Small published by Wiley-VCH GmbH.
Références
L. Wilson, L. Horton, K. Kunzmann, B. J. Sahakian, V. F. J. Newcombe, E. A. Stamatakis, N. von Steinbuechel, K. Cunitz, A. Covic, A. Maas, D. V. Praag, D. Menon, J. Neurol. Neurosurg. Psychiatry. 2021, 92, 407.
D. H. Smith, V. E. Johnson, W. Stewart, Nat. Rev. Neurol. 2013, 9, 211.
S. Kabadi, A. Faden, Int. J. Mol. Sci. 2014, 15, 1216.
R. Alyautdin, I. Khalin, M. I. Nafeeza, M. H. Haron, D. Kuznetsov, Int. J. Nanomedicine 2014, 9, 795.
M. J. Mitchell, M. M. Billingsley, R. M. Haley, M. E. Wechsler, N. A. Peppas, R. Langer, Nat. Rev. Drug Discovery 2021, 20, 101.
W. Li, J. Qiu, X.-L. Li, S. Aday, J. Zhang, G. Conley, J. Xu, J. Joseph, H. Lan, R. Langer, R. Mannix, J. M. Karp, N. Joshi, Sci. Adv. 2021, 7, eabd6889.
L. J. Cruz, M. A. Stammes, I. Que, E. R. Van Beek, V. T. Knol-Blankevoort, T. J. A. Snoeks, A. Chan, E. L. Kaijzel, C. W. G. M. Löwik, J. Control Release 2016, 223, 31.
E. J. Kwon, M. Skalak, R. Lo Bu, S. N. Bhatia, ACS Nano 2016, 10, 7926.
D. Yoo, A. W. Magsam, A. M. Kelly, P. S. Stayton, F. M. Kievit, A. J. Convertine, ACS Nano 2017, 11, 8600.
I. Khalin, R. Alyautdin, T. W. Wong, J. Gnanou, G. Kocherga, J. Kreuter, Drug Delivery 2016, 23, 3520.
I. Khalin, D. Heimburger, N. Melnychuk, M. Collot, B. Groschup, F. Hellal, A. Reisch, N. Plesnila, A. S. Klymchenko, ACS Nano 2020, 14, 9755.
P. Henrich-Noack, D. Nikitovic, M. Neagu, A. O. Docea, A. B. Engin, S. Gelperina, M. Shtilman, P. Mitsias, G. Tzanakakis, I. Gozes, A. Tsatsakis, Nanomedicine 2019, 17, 359.
L. L. Israel, A. Galstyan, E. Holler, J. Y. Ljubimova, J. Controlled Release 2020, 320, 45.
J. Kreuter, Adv. Drug Delivery Rev. 2014, 71, 2.
A. B. Vogel, I. Kanevsky, Y. Che, K. A. Swanson, A. Muik, M. Vormehr, L. M. Kranz, K. C. Walzer, S. Hein, A. Güler, J. Loschko, M. S. Maddur, A. Ota-Setlik, K. Tompkins, J. Cole, B. G. Lui, T. Ziegenhals, A. Plaschke, D. Eisel, S. C. Dany, S. Fesser, S. Erbar, F. Bates, D. Schneider, B. Jesionek, B. Sänger, A.-K. Wallisch, Y. Feuchter, H. Junginger, S. A. Krumm, et al., Nature 2021, 592, 283.
D. M. Teleanu, C. Chircov, A. M. Grumezescu, R. I. Teleanu, Pharmaceutics 2019, 11, 101.
N. Anton, J. -. P. Benoit, P. Saulnier, J. Control Release 2008, 128, 185.
A. S. Klymchenko, F. Liu, M. Collot, N. Anton, Adv. Healthcare Mater. 2021, 10, 2001289.
J. Marschallinger, T. Iram, M. Zardeneta, S. E. Lee, B. Lehallier, M. S. Haney, J. V. Pluvinage, V. Mathur, O. Hahn, D. W. Morgens, J. Kim, J. Tevini, T. K. Felder, H. Wolinski, C. R. Bertozzi, M. C. Bassik, L. Aigner, T. Wyss-Coray, Nat. Neurosci. 2020, 23, 194.
A. S. Klymchenko, E. Roger, N. Anton, H. Anton, I. Shulov, J. Vermot, Y. Mely, T. F. Vandamme, RSC Adv. 2012, 2, 11876.
A. Reisch, P. Didier, L. Richert, S. Oncul, Y. Arntz, Y. Mély, A. S. Klymchenko, Nat. Commun. 2014, 5, 4089.
B. Andreiuk, A. Reisch, E. Bernhardt, A. S. Klymchenko, Chem. Asian J. 2019, 14, 836.
I. Khalin, C. Severi, D. Heimburger, A. Wehn, F. Hellal, A. Reisch, A. S. Klymchenko, N. Plesnila, Nanomedicine: Nanotechnol., Biol. Med. 2022, 40, 102511.
V. N. Kilin, H. Anton, N. Anton, E. Steed, J. Vermot, T. F. Vandamme, Y. Mely, A. S. Klymchenko, Biomaterials 2014, 35, 4950.
R. Bouchaala, L. Mercier, B. Andreiuk, Y. Mély, T. Vandamme, N. Anton, J. G. Goetz, A. S. Klymchenko, J. Control Release 2016, 236, 57.
N. Anton, T. F. Vandamme, Pharm. Res. 2011, 28, 978.
C. Xu, W. W. Webb, J. Opt. Soc. Am. B 1996, 13, 481.
J. S. Jeon, S. Bersini, J. A. Whisler, M. B. Chen, G. Dubini, J. L. Charest, M. Moretti, R. D. Kamm, Integ. Biology: Quant. Biosci. Nano Macro 2014, 6, 555.
A. C. Wehn, I. Khalin, M. Duering, F. Hellal, C. Culmsee, P. Vandenabeele, N. Plesnila, N. A. Terpolilli, Acta Neuropathol. Commun. 2021, 9, 138.
S. M. Schwarzmaier, S.-W. Kim, R. Trabold, N. Plesnila, J. Neurotrauma 2010, 27, 121.
H.-M. Wu, S.-C. Huang, P. Vespa, D. A. Hovda, M. Bergsneider, J. Neurotrauma 2013, 30, 352.
P. Mastorakos, N. Mihelson, M. Luby, S. R. Burks, K. Johnson, A. W. Hsia, J. Witko, J. A. Frank, L. Latour, D. B. Mcgavern, Nat. Neurosci. 2021, 24, 245.
G. Kislinger, H. Gnägi, M. Kerschensteiner, M. Simons, T. Misgeld, M. Schifferer, STAR Protoc. 2020, 1, 100232.
T. Karstens, K. Kobs, J. Phys. Chem. 1980, 84, 1871.
S. Cheng, X. Mao, X. Lin, A. Wehn, S. Hu, U. Mamrak, I. Khalin, M. Wostrack, F. Ringel, N. Plesnila, N. A. Terpolilli, J. Neurotrauma 2021, 1, 1572.
C. Kilkenny, W. J. Browne, I. C. Cuthill, M. Emerson, D. G. Altman, PLoS Biol. 2010, 8, e1000412.
J. Guillen, J. Am. Assoc. Lab. Anim. Sci. 2012, 51, 311.
M. Ghosh, M. Balbi, F. Hellal, M. Dichgans, U. Lindauer, N. Plesnila, Ann. Neurol. 2015, 78, 887.
K. Young, H. Morrison, J. Vis Exp. 2018, 5, 57648.
A. Karperien, FracLac for ImageJ. 1999-2013.
M. D. M. Fernández-Arjona, J. M. Grondona, P. Granados-Durán, P. Fernández-Llebrez, M. D. López-Ávalos, Front. Cell Neurosci. 2017, 11, 235.
J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.- Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, A. Cardona, Nat. Methods 2012, 9, 676.
D. R. Berger, H. S. Seung, J. W. Lichtman, Front. Neural Circuits 2018, 12, 88.
A. Brito, Blender Quick Start Guide: 3D Modeling, Animation, and Render with Eevee in Blender 2.8., Packt Publishing 2018.
M. Nowak, M. E. Helgeson, S. Mitragotri, Adv. Ther. 2020, 3, 1900073.
L. E. Waggoner, M. I. Madias, A. A. Hurtado, E. J. Kwon, AAPS J. 2021, 23, 100.
V. N. Bharadwaj, J. Lifshitz, P. D. Adelson, V. D. Kodibagkar, S. E. Stabenfeldt, Sci. Rep. 2016, 6, 29988.
R. Münter, K. Kristensen, D. Pedersbaek, J. B. Larsen, J. B. Simonsen, T. L. Andresen, Nanoscale 2018, 10, 22720.
N. Hoshyar, S. Gray, H. Han, G. Bao, Nanomedicine 2016, 11, 673.
S. C. Stein, D. I. Graham, X.-H. Chen, D. H. Smith, Neurosurgery 2004, 54, 687.
S. C. Stein, X.-H. Chen, G. P. Sinson, D. H. Smith, J. Neurosurgery 2002, 97, 1373.
S. M. Schwarzmaier, C. De Chaumont, M. Balbi, N. A. Terpolilli, C. Kleinschnitz, A. Gruber, N. Plesnila, J. Neurotrauma 2016, 33, 1634.
C. Albert-Weissenberger, S. Hopp, B. Nieswandt, A.-L. Sirén, C. Kleinschnitz, C. Stetter, J. Neuroimmunol. 2019, 326, 9.
D. Lu, A. Mahmood, A. Goussev, C. Qu, Z. G. Zhang, M. Chopp, J Neurotrauma 2004, 21, 1756.
A. Zinger, S. Soriano, G. Baudo, E. D. Rosa, F. Taraballi, S. Villapol, Adv. Funct. Mater. 2021, 31, 2100722.
D. K. Sandsmark, A. Bashir, C. L. Wellington, R. Diaz-Arrastia, Neuron 2019, 103, 367.
Y. Wu, H. Wu, X. Guo, B. Pluimer, Z. Zhao, Front. Physiol. 2020, 11, 1030.
S. M. Schwarzmaier, M. Gallozzi, N. Plesnila, J. Neurotrauma 2015, 32, 990.
K. Zweckberger, N. Plesnila, Neurosci. Lett. 2009, 454, 115.
N. Plesnila, J. Schulz, M. Stoffel, J. Eriskat, D. Pruneau, A. Baethmann, J. Neurotrauma 2001, 18, 1049.
M. Krueger, I. Bechmann, K. Immig, A. Reichenbach, W. Härtig, D. Michalski, J. Cereb. Blood Flow Metab. 2015, 35, 292.
S. Egloff, A. Runser, A. Klymchenko, A. Reisch, Small Methods 2021, 5, 2000947.
E. T. Ahrens, J. W. M. Bulte, Nat. Rev. Immunol. 2013, 13, 755.
Z. Wang, C. Tiruppathi, R. D. Minshall, A. B. Malik, ACS Nano 2009, 3, 4110.
S. A. Predescu, D. N. Predescu, A. B. Malik, Am. J. Physiol. 2007, 293, L823.
P. Kamali-Zare, C. Nicholson, Basic Clin. Neurosci. 2013, 4, 282.
R. G. Thorne, C. Nicholson, Proc. Natl. Acad. Sci. USA 2006, 103, 5567.
Y. Y. Chen, A. M. Syed, P. MacMillan, J. V. Rocheleau, W. C. W. Chan, Adv. Mater. 2020, 32, 1906274.
B. J. Boyd, A. Galle, M. Daglas, J. V. Rosenfeld, R. Medcalf, J. Drug Targeting 2015, 23, 847.