Fig. 3.

Targeted delivery of oligonucleotide polyconjugates to liver hepatocytes in mice. Shown are confocal images of liver sections from mice injected i.v. with polyconjugate covalently linked through a CDM linkage to the targeting ligand NAG (A and D) or to mannose (B) or glucose (C) as controls. Cy3-labeled 21-mer dsDNA (red) was covalently attached to polyconjugate through a disulfide linkage (A–C) or was present in a noncovalent complex with polyconjugate (D). Livers were harvested 1 h after injection, fixed, and counterstained with ToPro-3 to visualize nuclei (blue) and Alexa 488 phalloidin to visualize cell outlines (green). Each image comprised a flattened projection of 11 optical images (0.4 μm each) to represent combined fluorescence signals from a 4-μm-thick section. Asterisks mark representative hepatocytes, and arrows indicate representative nonparenchymal cells.