Multiomics analysis of naturally efficacious lipid nanoparticle coronas reveals high-density lipoprotein is necessary for their function

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 and Alan Sabirsh ()
Additional contact information
Kai Liu: Pharmaceutical Sciences, R&D, AstraZeneca
Ralf Nilsson: BioPharmaceuticals R&D, AstraZeneca
Elisa Lázaro-Ibáñez: Pharmaceutical Sciences, R&D, AstraZeneca
Hanna Duàn: Pharmaceutical Sciences, R&D, AstraZeneca
Tasso Miliotis: BioPharmaceuticals R&D, AstraZeneca
Marie Strimfors: BioPharmaceuticals R&D, AstraZeneca
Michael Lerche: Pharmaceutical Sciences, R&D, AstraZeneca
Ana Rita Salgado Ribeiro: Pharmaceutical Sciences, R&D, AstraZeneca
Johan Ulander: Pharmaceutical Sciences, R&D, AstraZeneca
Daniel Lindén: BioPharmaceuticals R&D, AstraZeneca
Anna Salvati: University of Groningen
Alan Sabirsh: Pharmaceutical Sciences, R&D, AstraZeneca

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-39768-9

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