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  • Title: Synthesis of novel cholesterol-based ionizable lipids for mRNA delivery.
    Author: Qian R, Ullah A, Cui J, Cai X, Cao J, Wu L, Shen S.
    Journal: Colloids Surf B Biointerfaces; 2024 Aug; 240():113980. PubMed ID: 38781845.
    Abstract:
    The safe and effective delivery of messenger ribonucleic acid (mRNA) is crucial for its therapeutic effects in vivo. In this study, we developed a new type of ionizable lipid S-1, which contains an amino head, a cholesterol matrix, and a long hydrophobic carbon tail. We employed microfluidics to rapidly mix an ethanol phase containing S-1 lipid with an aqueous mRNA to form mRNA/S-1 lipid nanoparticles (LNPs, 100-200 nm). We observed low cytotoxicity and high transfection efficiency in RAW264.7 and HCT-116 cell lines for mRNA/S-1 LNPs, comparable to mRNA/SM-102 LNPs. Based on the obtained findings, mRNA/S-1 LNPs have good stability, low cytotoxicity, high transfection efficiency, and enhanced cellular uptake. The synthesized S-1 lipid ensures efficient assembly of lipid nanoparticles, protects mRNA from RNase degradation, and enables the delivery of mRNA into the cytoplasm for translation.
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