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CF3-2N6-UC18

Version 1.f7a682ee · 2026-09-13

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CAS No.Not available
Chemical NameCF3-2N6-UC18
SynonymsCF32N6UC18, CF3 2N6 UC18
SMILESCCCCCCCC/C=C\CCCCCCCCN(CCCCCCCC)CCCCCCNC1=CC=NC2=C1C=CC(C(F)(F)F)=C2
FormulaC53H92F3N3
M.Wt828.34
PurityELSD-HPLC>95%
StorageOriginal product: up to 1 year under the storage conditions stated on the vial, kept tightly sealed. Stock solutions: aliquots at -20°C, generally up to one month.
Shipping conditionShips from Shanghai. Pure lipid is stable during ice-pack transport.
PublicationStructure-guided design of endosomolytic chloroquine-like lipid nanoparticles for mRNA delivery and genome editing-Nature Communications volume 16, Article number: 4241 (2025)

CF3-2N6-UC18​​ is a rationally designed chloroquine-inspired ionizable lipid that enables robust mRNA delivery and genome editing. It integrates three modular components: a 7-trifluoromethyl-substituted quinoline scaffold (mimicking chloroquine’s endosomolytic properties), a hexamethylenediamine linker with two ionizable nitrogen atoms (pH-responsive protonation), and two unsaturated oleyl (C18:1) hydrophobic tails (enhancing membrane fusion and nanoparticle stability). This lipid self-assembles into ecoLNPs (endosomolytic chloroquine-like lipid nanoparticles) with spherical morphology (~200 nm diameter, 98% mRNA encapsulation). Its pH-sensitive activity triggers endosomal escape through dual mechanisms: ​​proton sponge effect​​ (buffering endo-lysosomal pH) and ​​saposin B-mediated membrane disruption​​ (molecular docking confirms chloroquine-like binding to lysosomal saposin B). In vitro, ecoLNPs outperform commercial reagents (18.9-fold higher mRNA delivery than Lipofectamine 2000) and penetrate 3D cell models. They resist serum/RNase degradation and retain >90% activity after 7-day storage at 4°C. In vivo, ecoLNPs achieve tissue-specific mRNA expression via multiple routes (intravenous, intramuscular, etc.), with strong lymph node tropism (90.2% after intramuscular injection) comparable to SM-102 LNPs (Moderna’s COVID-19 vaccine carrier). They mediate efficient Cre mRNA-driven recombination and CRISPR-Cas9 editing in transgenic mice. CF3-2N6-UC18’s modular design, stability, and dual endosomal escape strategies position it as a versatile platform for mRNA vaccines, gene therapy, and genome editing applications.

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