Interaction Kinetics of Individual mRNA-Containing Lipid Nanoparticles with an Endosomal Membrane Mimic: Dependence on pH, Protein Corona Formation, and Lipoprotein Depletion Научная публикация
| Журнал |
ACS Nano
ISSN: 1936-0851 , E-ISSN: 1936-086X |
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| Вых. Данные | Год: 2022, Том: 16, Номер: 12, Страницы: 20163–20173 Страниц : 11 DOI: 10.1021/acsnano.2c04829 | ||||||||
| Ключевые слова | endosomal membrane; ionizable lipid nanoparticle; lipoprotein; mRNA delivery; protein corona | ||||||||
| Авторы |
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| Организации |
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Информация о финансировании (1)
| 1 | Stiftelsen för strategisk forskning | IRC15-0065 |
Реферат:
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. © 2022 The Authors. Published by American Chemical Society.
Библиографическая ссылка:
Aliakbarinodehi N.
, Gallud A.
, Mapar M.
, Wesén E.
, Heydari S.
, Jing Y.
, Emilsson G.
, Liu K.
, Sabirsh A.
, Zhdanov V.P.
, Lindfors L.L.
, Esbjörner E.K.
, Höök F.
Interaction Kinetics of Individual mRNA-Containing Lipid Nanoparticles with an Endosomal Membrane Mimic: Dependence on pH, Protein Corona Formation, and Lipoprotein Depletion
ACS Nano. 2022. V.16. N12. P.20163–20173. DOI: 10.1021/acsnano.2c04829 WOS Scopus РИНЦ CAPlusCA PMID OpenAlex
Interaction Kinetics of Individual mRNA-Containing Lipid Nanoparticles with an Endosomal Membrane Mimic: Dependence on pH, Protein Corona Formation, and Lipoprotein Depletion
ACS Nano. 2022. V.16. N12. P.20163–20173. DOI: 10.1021/acsnano.2c04829 WOS Scopus РИНЦ CAPlusCA PMID OpenAlex
Даты:
| Поступила в редакцию: | 17 мая 2022 г. |
| Принята к публикации: | 6 дек. 2022 г. |
| Опубликована online: | 13 дек. 2022 г. |
| Опубликована в печати: | 27 дек. 2022 г. |
Идентификаторы БД:
| Web of science: | WOS:000897267300001 |
| Scopus: | 2-s2.0-85144101490 |
| РИНЦ: | 54734450 |
| Chemical Abstracts: | 2022:3079851 |
| Chemical Abstracts (print): | 181:109002 |
| PMID (PubMed): | 36511601 |
| OpenAlex: | W4311282977 |