Construction of Spleen-Accumulated Polysorbate 20-Containing Ionizable Lipid Nanoparticles for mRNA Delivery.

ABSTRACT: Messenger RNA therapy represents a transformative therapeutic in vaccine development, tumor immunotherapy, and genetic disease intervention. Polyethylene glycol (PEG) lipid, a key component of ionizable lipid nanoparticles (iLNPs) for mRNA delivery, and the PEG antibodies induced by PEG are associated with hypersensitivity and accelerated blood clearance. To address the above PEG-associated challenges, we systematically investigated polysorbate 20 (PS20) as an alternative for constructing PEG-free iLNPs. The formulation of PS20-incorporated iLNPs (PS20-iLNPs) for carrying mRNA was systematically investigated by analyzing the particle size, pKa, endosomal escape efficiency, and cellular internalization efficiency of iLNPs with different molar ratio PS20 content (0.5-5.0%). iLNPs with a rela

SUBMITTER: Liu H 

PROVIDER: S-EPMC12735810 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature