Journal Article

FZJ-2020-03070

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Hybrid Biopolymer and Lipid Nanoparticles with Improved Transfection Efficacy for mRNA

Siewert, C. D. ; Haas, H. ; Cornet, V. ; Nogueira, S. S. ; Nawroth, T. ; Uebbing, L. ; Ziller, A. ; Al-Gousous, J. ; Radulescu, A.FZJ* ; Schroer, M. A. ; Blanchet, C. E. ; Svergun, D. I. ; Radsak, M. P. ; Sahin, U. ; Langguth, P. (Corresponding author)

2020
MDPI Basel

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Please use a persistent id in citations: http://hdl.handle.net/2128/25650  doi:10.3390/cells9092034

Abstract: 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

Keyword(s): Polymers, Soft Nano Particles and Proteins (1st) ; Soft Condensed Matter (2nd) ; Medicine (2nd)

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Contributing Institute(s):

1. JCNS-FRM-II (JCNS-FRM-II)
2. Neutronenstreuung (JCNS-1)
3. Heinz Maier-Leibnitz Zentrum (MLZ)

Research Program(s):

1. 6G4 - Jülich Centre for Neutron Research (JCNS) (POF3-623) (POF3-623)
2. 6G15 - FRM II / MLZ (POF3-6G15) (POF3-6G15)

Experiment(s):

1. KWS-2: Small angle scattering diffractometer (NL3ao)

Appears in the scientific report 2020

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Database coverage:
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