ArticleNanomaterials (Basel, Switzerland)2025
Construction of Spleen-Accumulated Polysorbate 20-Containing Ionizable Lipid Nanoparticles for mRNA Delivery.
Article in Nanomaterials (Basel, Switzerland), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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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 relative molar ratio of 2.5% were identified as the optimal mRNA delivery carrier. This carrier exhibited excellent resistance to serum protein adsorption capacity, with serum stability 1.3-fold higher than PEG-iLNPs. At high lipid concentrations (2.7 mg/mL), the cell viability of PS20-iLNPs was maintained at 91.1%, which was 1.07-fold higher than PEG-iLNPs. Under serum interference, PS20-iLNPs achieved a transfection efficiency of 46.5%, marking a 10.6% improvement over PEG-iLNPs under identical conditions. Notably, PS20-iLNPs exhibited 24 times higher spleen accumulation than PEG-iLNPs. These findings highlight PS20 as a viable PEG substitute for developing PEG-free spleen-accumulated mRNA delivery platforms with enhanced therapeutic potential.
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