Figure 3.

In vivo biodistribution of Cy5 labeled scsiRNA-loaded NIR-labeled RS800-(Non-)ManNP in liver fibrotic mice on the organ level. (A) CCl₄ liver fibrosis mouse model: BALB/c mice were gavaged three times weekly with escalating doses of CCl₄ over a period of 3.5 weeks. (B) FACS analysis of a liver single cell suspension obtained from healthy and liver fibrotic mice. Profibrotic CD206+ macrophages are significantly higher in fibrotic compared to healthy livers (n = 5 per group, ** p < 0.001). (C,E) NIR in vivo imaging of RS800-ManNP/NonNP loaded with Cy5-scsiRNA directly after injection (t = 0 h): Carrier and siRNA accumulated primarily in the fibrotic livers. (D,F) Corresponding ex vivo imaging of Cy5-scsiRNA-loaded RS800-NonNP in organs harvested 12 h after IV injection (organs of mice treated with PBS alone served as autofluorescence controls): both particles and their cargo accumulated primarily in the livers (Figure S1). (G,H) Quantification of ex vivo organ fluorescence as shown in extracted organs above. Both siRNA cargo and particles efficiently accumulated in the liver, while biodegraded particle fragments and siRNA were excreted via the kidneys.