Targeting microspheres and cells to polyethylene glycol-modified biological surfaces.

Abstract

It has previously been demonstrated that damaged arterial tissue can be acutely modified with protein-reactive polyethylene glycol (PEG) to block undesirable platelet deposition. This concept might be expanded by employing PEG-biotin and its strong interaction with avidin for site-specific targeted delivery. Toward this end, cultured endothelial cells (ECs) were surface modified with PEG-biotin and the available biotin was quantified with flow cytometry. NeutrAvidin-coated microspheres and PEG-biotin modified ECs with NeutrAvidin as a bridging molecule were delivered under arterial shear stress to PEG-biotin modified ECs on a coverslip as well as scrape-damaged bovine carotid arteries. After incubation with a 10 mM solution for 1 min, 8 x 10(7) PEG-biotin molecules/EC were found and persisted for up to 120 h. Perfused microspheres adhered to NHS-PEG-biotin treated bovine carotid arteries with 60 +/- 16 microspheres/mm(2) versus 11 +/- 4 microspheres/mm(2) for control arteries (p < 0.015). Similarly, 22 +/- 5 targeted ECs/mm(2) adhered to NHS-PEG-biotin treated bovine carotid arteries versus 6 +/- 2 ECs/mm(2) for control arteries (p < 0.01). The targeting strategy demonstrated here might ultimately find application for drug delivery, gene therapy, or cell therapy where localization to specific labeled vascular regions is desired following catheter-based or surgical procedures.