Fig. 6: Effects of unsaturated and carboxy-terminated lipid structures.

a Structures of the siRNA-lipid conjugates with varied lipid chemistries. b Cy5-labeled siRNA-lipid conjugates were delivered i.v. at 1 mg/kg. Intravascular Cy5 fluorescence was measured over ~1 h and used to calculate siRNA circulation half-life (n = 3–5). c Cy5 fluorescence in kidneys, lungs, liver, spleen, and heart was measured 1 h after treatment. Fluorescence values in kidneys relative to the total fluorescence values of all organs combined is shown (n = 3–5). d Size exclusion chromatographic calculation of fraction of Cy5 fluorescence associated with albumin-containing plasma fractions (n = 3–4). e Representative in vitro binding responses of siRNA conjugates to human serum albumin (400 nM) measured by biolayer interferometry. f Schematic showing treatment schedule for i.v. delivery of siRNA-lipid conjugates. Tumors collected on day 7 were dissociated, and tumor cells were assessed for Cy5 fluorescence by flow cytometry (n = 5–6) (g) or lysed and assessed for luciferase activity (n = 6) (h). Each bar represents the average value (± S.D.), and each point represents values measured for each independent tumor sample. For (b–c, g, h), significance was assigned using one-way ANOVA with Tukey’s multiple comparisons test. For d, significance was assigned using a Kruskal-Wallis test with Dunn’s multiple comparisons test.