Fig. 2: Design and characterization of tetrahydroisoquinoline alkaloid-based ionizable lipids.

a Chemical structures of lipid building blocks comprising five amine heads and 15 alkylated tails. b Optimization workflow for BE lipidoid molecule development, involving 27 formulations derived from 75 novel ionizable compounds. (Created with BioRender.com) c Affinities of various ionizable lipidoid molecules for poly(A) measured using fluorescence spectroscopy. d, e Cellular uptake of LNPs assessed by fluorescence co-localization studies and flow cytometry analysis. LNPs were labeled DiD (red). Nuclei were stained with Hoechst 33342 (blue). Scale bar, 20 µm. f In vivo imaging of mice after injection of LNP@DiR at 0.5, 1, 2, 4, and 8 h. g Ex vivo fluorescence distribution showing brain-to-liver ratio at 1 h. Data are presented as mean ± SD (n = 3 independent experiments). Statistical significance was determined by two-tailed unpaired Student’s t test (two groups) or one-way ANOVA with Dunnett’s multiple comparison tests (multiple groups); **P < 0.01, ***P < 0.001, ****P < 0.0001. Source data are provided as a Source Data file.