Abstract 1073: Nitric Oxide Improves Bifunctional Echogenic Immunoliposome Delivery into the Arterial Wall
Background: We have successfully demonstrated that nitric oxide (NO) containing echogenic immunoliposomes (ELIP) can enhance endothelial permeability. Bifunctional ELIP (BF-ELIP) can bind to stem cells, directing them to inflammatory components of atheroma. We hypothesized that NO can improve targeted delivery of BF-ELIP into the arterial wall.
Methods: Rhodamine-labeled NO-BF-ELIP composed of phospholipids and cholesterol were prepared and conjugated to antibodies specific for human/mouse ICAM-1 and CD34 via a thioether linkage. Carotid and femoral arteries of two Yucatan miniswine were collected and placed in to an ex vivo perfusion system. Acoustic enhancement of the arterial wall was monitored and imaged using a 40 MHz transducer (Vevo 770, VisualSonics Inc.) 5 minutes after each ELIP administration. The association of rhodamine-labeled BF-ELIP to the arterial wall was determined by fluorescent microscopy. NO-BF-ELIP was compared to non-specific binding (IgG-ELIP) and air-BF-ELIP.
Results: Both air-BF-ELIP and NO-BF-ELIP demonstrated increased penetration into the intimal and adventitial layers compared to baseline (p<0.05). Importantly, adventitial highlighting with NO-BF-ELIP was greater than air-BF-ELIP (p<0.05). Fluorescent microscopy confirmed increased NO-BF-ELIP infiltration into all components of the arterial wall compared to IgG-ELIP and air-BF-ELIP.
Conclusion: NO can effectively improve endothelial permeability thus facilitating BF-ELIP delivery to inflammatory components in the arterial wall. This methodology allows directed targeted stem cell delivery to active atheroma.