Fig. 4.

Targeting peptide and fusogenic uptake enhances homing to infected lungs and macrophages. a Immunofluorescent sections of major organs of healthy and infected Balb/C mice injected with FAM-CRV.peptide (green). Blue indicates cell nuclei stained with DAPI, red indicates macrophages marked by F4/80 antibody stain. b Quantified fluorescence signals (IVIS 200) from organs of healthy and infected Balb/C mice injected with fusogenic nanoparticles containing DiI membrane stain and siIrf5 payload, with either a non-targeting (F-siIRF5-mPEG) or the CRV targeting group (F-siIRF5-CRV) at doses of 23.2 µmol/kg lipid, 24 µg/kg siRNA, 0.5 mg/kg pSi. “H-24” indicates healthy Balb/C organs "collected 24 h post treatment; “I-1” indicates Balb/C organs of infected harvested 1 h post; treatment; and “I-24” indicates infected Balb/C organs 24 h post-" treatment. Error bars indicate SD. Data are representative of n = 3, quantified by ImageJ analyses. c–f Confocal microscope images of DiI-loaded fusogenic and non-fusogenic nanoparticles homed to infected lung with pendant CRV targeting peptide. These nanoparticles contained no siIrf5 payload; green indicates macrophages (FITC-tagged rat anti-mouse F4/80 stain), red indicates lipophilic DiI from nanoparticles; c lung of healthy mouse injected with F-DiI-CRV; d lung of infected mouse injected with PBS control; e lung of infected mouse injected with NF-DiI-CRV; f lung of infected mouse injected with F-DiI-CRV. The data show DiI from the fusogenic, CRV-targeted nanoparticles is strongly co-localized with macrophages