Multiomics analysis of naturally efficacious lipid nanoparticle coronas reveals high-density lipoprotein is necessary for their function
Abstract In terms of lipid nanoparticle (LNP) engineering, the relationship between particle composition, delivery efficacy, and the composition of the biocoronas that form around LNPs, is poorly understood. To explore this we analyze naturally efficacious biocorona compositions using an unbiased sc...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-39768-9 |
| _version_ | 1797784551049658368 |
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| author | Kai Liu Ralf Nilsson Elisa Lázaro-Ibáñez Hanna Duàn Tasso Miliotis Marie Strimfors Michael Lerche Ana Rita Salgado Ribeiro Johan Ulander Daniel Lindén Anna Salvati Alan Sabirsh |
| author_facet | Kai Liu Ralf Nilsson Elisa Lázaro-Ibáñez Hanna Duàn Tasso Miliotis Marie Strimfors Michael Lerche Ana Rita Salgado Ribeiro Johan Ulander Daniel Lindén Anna Salvati Alan Sabirsh |
| author_sort | Kai Liu |
| collection | DOAJ |
| description | Abstract In terms of lipid nanoparticle (LNP) engineering, the relationship between particle composition, delivery efficacy, and the composition of the biocoronas that form around LNPs, is poorly understood. To explore this we analyze naturally efficacious biocorona compositions using an unbiased screening workflow. First, LNPs are complexed with plasma samples, from individual lean or obese male rats, and then functionally evaluated in vitro. Then, a fast, automated, and miniaturized method retrieves the LNPs with intact biocoronas, and multiomics analysis of the LNP-corona complexes reveals the particle corona content arising from each individual plasma sample. We find that the most efficacious LNP-corona complexes were enriched with high-density lipoprotein (HDL) and, compared to the commonly used corona-biomarker Apolipoprotein E, corona HDL content was a superior predictor of in-vivo activity. Using technically challenging and clinically relevant lipid nanoparticles, these methods reveal a previously unreported role for HDL as a source of ApoE and, form a framework for improving LNP therapeutic efficacy by controlling corona composition. |
| first_indexed | 2024-03-13T00:41:30Z |
| format | Article |
| id | doaj.art-41ddf1ba8b124addb8c13982c9688b78 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-13T00:41:30Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-41ddf1ba8b124addb8c13982c9688b782023-07-09T11:18:13ZengNature PortfolioNature Communications2041-17232023-07-0114111610.1038/s41467-023-39768-9Multiomics analysis of naturally efficacious lipid nanoparticle coronas reveals high-density lipoprotein is necessary for their functionKai Liu0Ralf Nilsson1Elisa Lázaro-Ibáñez2Hanna Duàn3Tasso Miliotis4Marie Strimfors5Michael Lerche6Ana Rita Salgado Ribeiro7Johan Ulander8Daniel Lindén9Anna Salvati10Alan Sabirsh11Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZenecaTranslational Science and Experimental Medicine, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZenecaAdvanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZenecaAdvanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZenecaTranslational Science and Experimental Medicine, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZenecaBioscience Metabolism, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZenecaAdvanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZenecaAdvanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZenecaData Science and Modelling, Pharmaceutical Sciences, R&D, AstraZenecaBioscience Metabolism, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZenecaDepartment of Nanomedicine & Drug Targeting, Groningen Research Institute of Pharmacy, University of GroningenAdvanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZenecaAbstract In terms of lipid nanoparticle (LNP) engineering, the relationship between particle composition, delivery efficacy, and the composition of the biocoronas that form around LNPs, is poorly understood. To explore this we analyze naturally efficacious biocorona compositions using an unbiased screening workflow. First, LNPs are complexed with plasma samples, from individual lean or obese male rats, and then functionally evaluated in vitro. Then, a fast, automated, and miniaturized method retrieves the LNPs with intact biocoronas, and multiomics analysis of the LNP-corona complexes reveals the particle corona content arising from each individual plasma sample. We find that the most efficacious LNP-corona complexes were enriched with high-density lipoprotein (HDL) and, compared to the commonly used corona-biomarker Apolipoprotein E, corona HDL content was a superior predictor of in-vivo activity. Using technically challenging and clinically relevant lipid nanoparticles, these methods reveal a previously unreported role for HDL as a source of ApoE and, form a framework for improving LNP therapeutic efficacy by controlling corona composition.https://doi.org/10.1038/s41467-023-39768-9 |
| spellingShingle | Kai Liu Ralf Nilsson Elisa Lázaro-Ibáñez Hanna Duàn Tasso Miliotis Marie Strimfors Michael Lerche Ana Rita Salgado Ribeiro Johan Ulander Daniel Lindén Anna Salvati Alan Sabirsh Multiomics analysis of naturally efficacious lipid nanoparticle coronas reveals high-density lipoprotein is necessary for their function Nature Communications |
| title | Multiomics analysis of naturally efficacious lipid nanoparticle coronas reveals high-density lipoprotein is necessary for their function |
| title_full | Multiomics analysis of naturally efficacious lipid nanoparticle coronas reveals high-density lipoprotein is necessary for their function |
| title_fullStr | Multiomics analysis of naturally efficacious lipid nanoparticle coronas reveals high-density lipoprotein is necessary for their function |
| title_full_unstemmed | Multiomics analysis of naturally efficacious lipid nanoparticle coronas reveals high-density lipoprotein is necessary for their function |
| title_short | Multiomics analysis of naturally efficacious lipid nanoparticle coronas reveals high-density lipoprotein is necessary for their function |
| title_sort | multiomics analysis of naturally efficacious lipid nanoparticle coronas reveals high density lipoprotein is necessary for their function |
| url | https://doi.org/10.1038/s41467-023-39768-9 |
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