- Ionizable LNPs transformed nucleic acid therapeutics since 2018, yet extrahepatic delivery is hindered by rapid hepatic uptake driven by apolipoprotein adsorption.
- Accurate LNP protein corona analysis is essential for organ-specific tropism, but co-isolation of extracellular vesicles and lipoproteins masks true corona composition.
- Refined proteomic strategies and tailored investigative approaches are required, recognising LNP coronas differ from rigid shells of inorganic nanoparticles.
Nat Commun. 2026 Jun 12;17(1):5261. doi: 10.1038/s41467-026-74240-4.
ABSTRACT
Since 2018, ionizable lipid nanoparticles (LNPs) have revolutionized nucleic acid therapeutics. However, achieving potent extrahepatic delivery remains a formidable challenge, primarily due to rapid hepatic uptake driven by apolipoprotein adsorption. While analyzing the LNP protein corona is essential for engineering organ-specific tropism, these soft materials present unique analytical hurdles. Co-isolation of blood-borne contaminants, such as extracellular vesicles and lipoproteins, often masks the true corona composition. This perspective examines the critical need for refined proteomic strategies to distinguish genuine corona proteins from impurities. We propose tailored investigative approaches, suggesting the LNP protein corona significantly differs from the rigid shells observed on inorganic nanoparticles.
PMID:42285973 | DOI:10.1038/s41467-026-74240-4
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