Hybrid Biopolymer and Lipid Nanoparticles with Improved Transfection Efficacy for mRNA
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 diff...
| Autori principali: | , , , , , , , , , , , , , , |
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| Natura: | Articolo |
| Lingua: | English |
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MDPI AG
2020-09-01
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| Serie: | Cells |
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| Accesso online: | https://www.mdpi.com/2073-4409/9/9/2034 |
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| author | Christian D. Siewert Heinrich Haas Vera Cornet Sara S. Nogueira Thomas Nawroth Lukas Uebbing Antje Ziller Jozef Al-Gousous Aurel Radulescu Martin A. Schroer Clement E. Blanchet Dmitri I. Svergun Markus P. Radsak Ugur Sahin Peter Langguth |
| author_facet | Christian D. Siewert Heinrich Haas Vera Cornet Sara S. Nogueira Thomas Nawroth Lukas Uebbing Antje Ziller Jozef Al-Gousous Aurel Radulescu Martin A. Schroer Clement E. Blanchet Dmitri I. Svergun Markus P. Radsak Ugur Sahin Peter Langguth |
| author_sort | Christian D. Siewert |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T16:33:14Z |
| format | Article |
| id | doaj.art-ccd7af2a8e2e49719ca289339c9736b3 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T16:33:14Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-ccd7af2a8e2e49719ca289339c9736b32023-11-20T12:41:29ZengMDPI AGCells2073-44092020-09-0199203410.3390/cells9092034Hybrid Biopolymer and Lipid Nanoparticles with Improved Transfection Efficacy for mRNAChristian D. Siewert0Heinrich Haas1Vera Cornet2Sara S. Nogueira3Thomas Nawroth4Lukas Uebbing5Antje Ziller6Jozef Al-Gousous7Aurel Radulescu8Martin A. Schroer9Clement E. Blanchet10Dmitri I. Svergun11Markus P. Radsak12Ugur Sahin13Peter Langguth14Department of Pharmaceutics and Biopharmaceutics, Johannes Gutenberg University Mainz, D-55131 Mainz, GermanyBioNTech RNA Pharmaceuticals, D-55131 Mainz, GermanyDepartment of Pharmaceutics and Biopharmaceutics, Johannes Gutenberg University Mainz, D-55131 Mainz, GermanyBioNTech RNA Pharmaceuticals, D-55131 Mainz, GermanyDepartment of Pharmaceutics and Biopharmaceutics, Johannes Gutenberg University Mainz, D-55131 Mainz, GermanyDepartment of Pharmaceutics and Biopharmaceutics, Johannes Gutenberg University Mainz, D-55131 Mainz, GermanyDepartment of Pharmaceutics and Biopharmaceutics, Johannes Gutenberg University Mainz, D-55131 Mainz, GermanyDepartment of Pharmaceutics and Biopharmaceutics, Johannes Gutenberg University Mainz, D-55131 Mainz, GermanyJülich Centre for Neutron Science JCNS at Heinz Maier-Leibnitz Centrum MLZ, D-85748 Garching, GermanyEuropean Molecular Biology Laboratory EMBL Hamburg Outstation c/o Deutsches Elektronen Synchrotron DESY, 22603 Hamburg, GermanyEuropean Molecular Biology Laboratory EMBL Hamburg Outstation c/o Deutsches Elektronen Synchrotron DESY, 22603 Hamburg, GermanyEuropean Molecular Biology Laboratory EMBL Hamburg Outstation c/o Deutsches Elektronen Synchrotron DESY, 22603 Hamburg, GermanyIIIrd Dept. of Medicine, Johannes Gutenberg University Medical Center, Johannes Gutenberg University, D-55131 Mainz, GermanyBioNTech RNA Pharmaceuticals, D-55131 Mainz, GermanyDepartment of Pharmaceutics and Biopharmaceutics, Johannes Gutenberg University Mainz, D-55131 Mainz, GermanyHybrid 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.https://www.mdpi.com/2073-4409/9/9/2034vaccinationCovid-19cancer immunotherapyRNAcationic polymercationic lipid |
| spellingShingle | Christian D. Siewert Heinrich Haas Vera Cornet Sara S. Nogueira Thomas Nawroth Lukas Uebbing Antje Ziller Jozef Al-Gousous Aurel Radulescu Martin A. Schroer Clement E. Blanchet Dmitri I. Svergun Markus P. Radsak Ugur Sahin Peter Langguth Hybrid Biopolymer and Lipid Nanoparticles with Improved Transfection Efficacy for mRNA Cells vaccination Covid-19 cancer immunotherapy RNA cationic polymer cationic lipid |
| title | Hybrid Biopolymer and Lipid Nanoparticles with Improved Transfection Efficacy for mRNA |
| title_full | Hybrid Biopolymer and Lipid Nanoparticles with Improved Transfection Efficacy for mRNA |
| title_fullStr | Hybrid Biopolymer and Lipid Nanoparticles with Improved Transfection Efficacy for mRNA |
| title_full_unstemmed | Hybrid Biopolymer and Lipid Nanoparticles with Improved Transfection Efficacy for mRNA |
| title_short | Hybrid Biopolymer and Lipid Nanoparticles with Improved Transfection Efficacy for mRNA |
| title_sort | hybrid biopolymer and lipid nanoparticles with improved transfection efficacy for mrna |
| topic | vaccination Covid-19 cancer immunotherapy RNA cationic polymer cationic lipid |
| url | https://www.mdpi.com/2073-4409/9/9/2034 |
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