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dc.contributor.authorYasar, Hanzey
dc.contributor.authorBiehl, Alexander
dc.contributor.authorDe Rossi, Chiara
dc.contributor.authorKoch, Marcus
dc.contributor.authorMurgia, Xabi
dc.contributor.authorLoretz, Brigitta
dc.contributor.authorLehr, Claus-Michael
dc.date.accessioned2018-10-08T09:54:33Z
dc.date.available2018-10-08T09:54:33Z
dc.date.issued2018-09-19
dc.identifier.issn1477-3155
dc.identifier.pmid30231888
dc.identifier.doi10.1186/s12951-018-0401-y
dc.identifier.urihttp://hdl.handle.net/10033/621508
dc.description.abstractMessenger RNA (mRNA) has gained remarkable attention as an alternative to DNA-based therapies in biomedical research. A variety of biodegradable nanoparticles (NPs) has been developed including lipid-based and polymer-based systems for mRNA delivery. However, both systems still lack in achieving an efficient transfection rate and a detailed understanding of the mRNA transgene expression kinetics. Therefore, quantitative analysis of the time-dependent translation behavior would provide a better understanding of mRNA's transient nature and further aid the enhancement of appropriate carriers with the perspective to generate future precision nanomedicines with quick response to treat various diseases. A lipid-polymer hybrid system complexed with mRNA was evaluated regarding its efficiency to transfect dendritic cells (DCs) by simultaneous live cell video imaging of both particle uptake and reporter gene expression. We prepared and optimized NPs consisting of poly (lactid-co-glycolid) (PLGA) coated with the cationic lipid 1, 2-di-O-octadecenyl-3-trimethylammonium propane abbreviated as LPNs. An earlier developed polymer-based delivery system (chitosan-PLGA NPs) served for comparison. Both NPs types were complexed with mRNA-mCherry at various ratios. While cellular uptake and toxicity of either NPs was comparable, LPNs showed a significantly higher transfection efficiency of ~ 80% while chitosan-PLGA NPs revealed only ~ 5%. Further kinetic analysis elicited a start of protein translation after 1 h, with a maximum after 4 h and drop of transgene expression after 48 h post-transfection, in agreement with the transient nature of mRNA. Charge-mediated complexation of mRNA to NPs enables efficient and fast cellular delivery and subsequent protein translation. While cellular uptake of both NP types was comparable, mRNA transgene expression was superior to polymer-based NPs when delivered by lipid-polymer NPs.en_US
dc.rightsAttribution-NonCommercial-ShareAlike 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/us/*
dc.subjectCationic lipiden_US
dc.subjectChitosan-PLGAen_US
dc.subjectGene deliveryen_US
dc.subjectLive cell imagingen_US
dc.subjectTransfectionen_US
dc.subjectmRNAen_US
dc.titleKinetics of mRNA delivery and protein translation in dendritic cells using lipid-coated PLGA nanoparticles.en_US
dc.typeArticleen_US
dc.contributor.departmentHIPS, Helmholtz-Institut für pharmazeutische Forschung Saarland, Universitätscampus 8.1, 66123 Saarbrücken, Germany.en_US
refterms.dateFOA2018-10-08T09:54:33Z
dc.source.journaltitleJournal of nanobiotechnology


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