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Interaction Kinetic...
Interaction Kinetics of Individual mRNA-Containing Lipid Nanoparticles with an Endosomal Membrane Mimic: Dependence on pH, Protein Corona Formation, and Lipoprotein Depletion
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- Aliakbarinodehi, Nima, 1986 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Gallud, Audrey, 1988 (author)
- Chalmers tekniska högskola,Chalmers University of Technology,AstraZeneca AB
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- Mapar, Mokhtar, 1983 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Vilhelmsson Wesén, Emelie, 1989 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Heydari, Sahar (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Jing, Yujia (author)
- AstraZeneca AB
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- Emilsson, Gustav, 1989 (author)
- AstraZeneca AB
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- Liu, Kai (author)
- AstraZeneca AB
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- Sabirsh, Alan (author)
- AstraZeneca AB
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- Zhdanov, Vladimir, 1952 (author)
- Russian Academy of Sciences,Chalmers tekniska högskola,Chalmers University of Technology
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- Lindfors, Lennart, 1961 (author)
- AstraZeneca AB
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- Esbjörner Winters, Elin, 1978 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Höök, Fredrik, 1966 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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(creator_code:org_t)
- 2022-12-13
- 2022
- English.
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In: ACS Nano. - : American Chemical Society (ACS). - 1936-086X .- 1936-0851. ; 16:12, s. 20163-20173
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https://doi.org/10.1...
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Abstract
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- Lipid nanoparticles (LNPs) have emerged as potent carriers for mRNA delivery, but several challenges remain before this approach can offer broad clinical translation of mRNA therapeutics. To improve their efficacy, a better understanding is required regarding how LNPs are trapped and processed at the anionic endosomal membrane prior to mRNA release. We used surface-sensitive fluorescence microscopy with single LNP resolution to investigate the pH dependency of the binding kinetics of ionizable lipid-containing LNPs to a supported endosomal model membrane. A sharp increase of LNP binding was observed when the pH was lowered from 6 to 5, accompanied by stepwise large-scale LNP disintegration. For LNPs preincubated in serum, protein corona formation shifted the onset of LNP binding and subsequent disintegration to lower pH, an effect that was less pronounced for lipoprotein-depleted serum. The LNP binding to the endosomal membrane mimic was observed to eventually become severely limited by suppression of the driving force for the formation of multivalent bonds during LNP attachment or, more specifically, by charge neutralization of anionic lipids in the model membrane due to their association with cationic lipids from earlier attached LNPs upon their disintegration. Cell uptake experiments demonstrated marginal differences in LNP uptake in untreated and lipoprotein-depleted serum, whereas lipoprotein-depleted serum increased mRNA-controlled protein (eGFP) production substantially. This complies with model membrane data and suggests that protein corona formation on the surface of the LNPs influences the nature of the interaction between LNPs and endosomal membranes.
Subject headings
- NATURVETENSKAP -- Kemi -- Fysikalisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Physical Chemistry (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biofysik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biophysics (hsv//eng)
Keyword
- mRNA delivery
- protein corona
- ionizable lipid nanoparticle
- lipoprotein
- endosomal membrane
Publication and Content Type
- art (subject category)
- ref (subject category)
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Aliakbarinodehi, ...
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Gallud, Audrey, ...
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Mapar, Mokhtar, ...
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Vilhelmsson Wesé ...
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Heydari, Sahar
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Jing, Yujia
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Emilsson, Gustav ...
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Liu, Kai
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Sabirsh, Alan
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Zhdanov, Vladimi ...
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Lindfors, Lennar ...
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Esbjörner Winter ...
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Höök, Fredrik, 1 ...
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NATURAL SCIENCES
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and Biological Scien ...
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NATURAL SCIENCES
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and Biophysics
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ACS Nano
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Chalmers University of Technology