Figure 5.

The PKCNs can deliver siRNA with high efficiency in vivo and the acid sensitivity of the PKCNs is critical for in vivo efficacy. Mice were injected with LPS (2.5 µg/kg) and GalN (700 mg/kg) i.p. to induce acute liver failure and injected with siRNA samples (3.5 µg/kg siRNA) via the jugular vein. Serum TNF-α concentration and ALT activity were measured at 24 h after treatment with siRNA samples. Significance of results was determined via the paired t-test between the PKCN–TNF-α siRNA and other delivery vehicles with P < 0.05 (asterisks). (A) The PKCNs reduced serum TNF-α values, whereas PLGA submicron particles had no effect. TNF-α concentration in the plasma was measured by ELISA (mean ± SE). (B) The PKCNs reduced serum ALT levels (mean ± SE), whereas PLGA submicron particles had no effect. (C) The PKCNs were localized in Kupffer cells. FITC-labeled F4/80 antibody (Pan macrophage marker) was used for Kupffer cell staining. DiI-loaded PKCNs (orange color) were taken up by Kupffer cells (green color) in vivo—white arrows. No PKCNs were found in hepatocytes—dark area (no green color). The picture was imaged by fluorescence microscopy (×20).