Fig. 4. Dendrimer localization and retention in activated glia in CP kits.

G4 dendrimer with various surface functionalities (red in all panels) were injected systemically in PND1 CP kits. Animals were euthanized and perfused with normal saline at 0.5 h, 4 h, or 24 h after administration into the lateral vein. (A) G4-OH-Cy5 is able to escape the blood vessels by 4 h and localize in activated glia cells (Iba+, green in all panels). By 24 h, any G4-OH-Cy5 dendrimer in the tissue and not in cells has been cleared. G4-NH₂-Cy5 remains in blood vessels at all time points studied, and does not localized in activated glia in the tissue parenchyma. G3.5-COOH-Cy5 shows delayed cellular uptake in the brain, with localization in the brain blood vessels at 4 h, but not at 0.5 h after injection. By 24 h, the G3.5-COOH-Cy5 is localized in activated microglia, but is sequestered in endosomes, whereas G4-OH-Cy5 is sequestered in late lysosomes. Cell nuclei are stained with DAPI (blue). All scale bars are 50 μm. (B) G4-OH, G3.5-COOH, and G4-NH₂ distribution in off-site organs in newborn kits with CP. Dendrimer accumulation in the heart, liver, lungs, and kidney as a function of time was measured following 55 mg/kg injection of G4-OH-Cy5, G3.5-COOH-Cy5, or G4-NH₂-Cy5 in newborn kits with CP. Data is represented as the percent injected dose (%ID) of dendrimer per gram of tissue. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)