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Open AccessArticle

Hybrid Biopolymer and Lipid Nanoparticles with Improved Transfection Efficacy for mRNA

1
Department of Pharmaceutics and Biopharmaceutics, Johannes Gutenberg University Mainz, D-55131 Mainz, Germany
2
BioNTech RNA Pharmaceuticals, D-55131 Mainz, Germany
3
Jülich Centre for Neutron Science JCNS at Heinz Maier-Leibnitz Centrum MLZ, D-85748 Garching, Germany
4
European Molecular Biology Laboratory EMBL Hamburg Outstation c/o Deutsches Elektronen Synchrotron DESY, 22603 Hamburg, Germany
5
IIIrd Dept. of Medicine, Johannes Gutenberg University Medical Center, Johannes Gutenberg University, D-55131 Mainz, Germany
6
Exp. Oncology, IIIrd Dept. of Medicine, TRON, Johannes Gutenberg University Medical Center, Johannes Gutenberg University, D-55131 Mainz, Germany
*
Author to whom correspondence should be addressed.
Cells 2020, 9(9), 2034; https://doi.org/10.3390/cells9092034
Received: 2 August 2020 / Revised: 1 September 2020 / Accepted: 2 September 2020 / Published: 5 September 2020
(This article belongs to the Special Issue Nanoparticles in Cancer Immunotherapy)
Hybrid nanoparticles from lipidic and polymeric components were assembled to serve as vehicles for the transfection of messenger RNA (mRNA) using different portions of the cationic lipid DOTAP (1,2-Dioleoyl-3-trimethylammonium-propane) and the cationic biopolymer protamine as model systems. Two different sequential assembly approaches in comparison with a direct single-step protocol were applied, and molecular organization in correlation with biological activity of the resulting nanoparticle systems was investigated. Differences in the structure of the nanoparticles were revealed by thorough physicochemical characterization including small angle neutron scattering (SANS), small angle X-ray scattering (SAXS), and cryogenic transmission electron microscopy (cryo-TEM). All hybrid systems, combining lipid and polymer, displayed significantly increased transfection in comparison to lipid/mRNA and polymer/mRNA particles alone. For the hybrid nanoparticles, characteristic differences regarding the internal organization, release characteristics, and activity were determined depending on the assembly route. The systems with the highest transfection efficacy were characterized by a heterogenous internal organization, accompanied by facilitated release. Such a system could be best obtained by the single step protocol, starting with a lipid and polymer mixture for nanoparticle formation. View Full-Text
Keywords: vaccination; Covid-19; cancer immunotherapy; RNA; cationic polymer; cationic lipid; lipid-polymer hybrid nanoparticles; small angle scattering vaccination; Covid-19; cancer immunotherapy; RNA; cationic polymer; cationic lipid; lipid-polymer hybrid nanoparticles; small angle scattering
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MDPI and ACS Style

Siewert, C.D.; Haas, H.; Cornet, V.; Nogueira, S.S.; Nawroth, T.; Uebbing, L.; Ziller, A.; Al-Gousous, J.; Radulescu, A.; Schroer, M.A.; Blanchet, C.E.; Svergun, D.I.; Radsak, M.P.; Sahin, U.; Langguth, P. Hybrid Biopolymer and Lipid Nanoparticles with Improved Transfection Efficacy for mRNA. Cells 2020, 9, 2034. https://doi.org/10.3390/cells9092034

AMA Style

Siewert CD, Haas H, Cornet V, Nogueira SS, Nawroth T, Uebbing L, Ziller A, Al-Gousous J, Radulescu A, Schroer MA, Blanchet CE, Svergun DI, Radsak MP, Sahin U, Langguth P. Hybrid Biopolymer and Lipid Nanoparticles with Improved Transfection Efficacy for mRNA. Cells. 2020; 9(9):2034. https://doi.org/10.3390/cells9092034

Chicago/Turabian Style

Siewert, Christian D.; Haas, Heinrich; Cornet, Vera; Nogueira, Sara S.; Nawroth, Thomas; Uebbing, Lukas; Ziller, Antje; Al-Gousous, Jozef; Radulescu, Aurel; Schroer, Martin A.; Blanchet, Clement E.; Svergun, Dmitri I.; Radsak, Markus P.; Sahin, Ugur; Langguth, Peter. 2020. "Hybrid Biopolymer and Lipid Nanoparticles with Improved Transfection Efficacy for mRNA" Cells 9, no. 9: 2034. https://doi.org/10.3390/cells9092034

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