Fig. 7: PLGA decoy pre-administration significantly enhances PCSK9 knockdown by PACE siRNA NPs in hepatocytes.

a Schematic of PLGA NP decoy pre-administration scheme with PCSK9 siRNA-loaded PACE NPs and in vivo assessment workflow. b Schematic of liver and blood end-point analyses to assess PCSK9 activity. c %PCSK9 mRNA knockdown as measured by quantitative RT-PCR in hepatocytes of PACE PCSK9 siRNA NP-treated mice and PACE PCSK9 siRNA NP-treated mice following PLGA NP pre-administration (n = 6 mice per group per population; error bars represent standard error of the mean (SEM)). An unpaired two-tailed t test was used for statistical analysis; p = 0.000000024, t = 15.601510, df = 10. d Cholesterol levels in untreated control, PACE PCSK9 siRNA NP-treated mice, and PACE PCSK9 siRNA NP-treated mice following PLGA NP pre-administration (n = 3 mice per group per population; error bars represent SEM). An ordinary one-way ANOVA was used for statistical analysis (F = 11.85, R² = 0.7980, p = 0.0082) with Holm-Šídák’s post-test for multiple comparisons; for untreated control (CTL) vs. PLGA + PACE NPs, p = 0.0084. e Representative epifluorescence liver image from three independent experiments of dye-loaded PLGA NP-treated animals 24 h post-IV administration. Nuclei are shown in blue, F4/80⁺ macrophages are shown in green, and PLGA NPs are shown in red. Scale bar, 100 μm.