Figure 8. Role of geometry on the functional therapeutic activity of anti-ICAM carriers.

(a) Induction of oxidative injury in HUVECs with 5 mmol/l H₂O₂ after delivery of antioxidant catalase by 0.1 versus 1 μm spherical anti-ICAM particles. Cell survival was estimated by labeling HUVECs with Live/Dead assay and fluorescent imaging. Data are mean ± SEM (n ≥ 500 cells/condition). The continuous and dashed lines in the graph represent survival levels of noninjured cells and H₂O₂-treated cells, respectively, tested after incubation with control 0.1 μm anti-ICAM particles. (b) Aberrant storage of sphingomyelin (SM), typical of the lysosomal storage disorder type A and B Niemann–Pick disease, was induced in HUVECs by treatment with 50 μmol/l imipramine. SM was labeled in these deficient cells by incubation for 16 hours at 37 °C with a BODIPY-FL_C12-SM analog. Reduction of SM within these intracellular compartments was imaged after internalization of recombinant acid sphingomyelinase, delivered by either 0.1 versus 1 μm spherical anti-ICAM carriers. Intracellular level of SM was quantified by fluorescence microscopy, and normalized to SM levels in normal HUVECs versus diseased HUVECs before enzyme replacement. Data are mean ± SEM (n ≥ 10 cells, two assays). ICAM, intercellular-adhesion molecule 1.