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Abstract
Replacing 10 mol % of a specific lipid in lipid nanoparticles (LNPs) significantly alters their structure and behavior.
- Subtle changes in LNP surface lipids can reshape the ApoE-LNP structure and its intracellular trafficking.
- ApoE binding to LNPs induces irregular membrane shapes when certain lipids are replaced.
- These structural changes impact receptor-mediated uptake and enhance endosomal disruption.
- Alterations lead to increased release of siRNA into the cytosol and may trigger cell apoptosis.
- ApoE is associated with promoting intracellular disassembly of LNPs.
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