(507g) Design and In Vitro Characterization of Polymer Vesicles with Adhesive Properties That Mimic Leukocytes

Cell sized polymer vesicles self-assembled from amphiphilic polymers are ideal platforms on which to design in vivo drug delivery, imaging, or cellular therapeutics. Increased bilayer thickness leads to tougher vesicles and larger hydrophobic bilayer cores in which to carry cargo compared to analogous phospholipids vesicles. Additionally, the use of synthetic materials allows for both simple tuning of membrane properties and easy attachment of targeting ligand to the exterior surface of vesicles. In this study we functionalize the surface of polybutadiene-polyethylene oxide based vesicles with anti-ICAM-1 antibody and sialyl Lewisx in order to mimic the adhesive characteristics of activated leukocytes which bind to the targets of these ligands, ICAM-1 integrin and selectins. We chose these targeting ligands because activated leukocytes adhere to sites of inflammation in blood vessel endothelium, and by delivering vesicles to areas of inflammation, we target sites of infection, inflammatory disease, and cancer. We used a modular biotin-avidin system to functionalize the vesicles, and we characterized the surfaces of these vesicles using confocal microscopy and flow cytometry. Using parallel plate flow chamber assay at typical post-capillary venule shear rates and MATLAB-based particle tracking, we show that these vesicles mimic the rolling to firm adhesion trajectories of leukocytes. This study shows that we can mimic the adhesive characteristics of a leukocyte under flow with a cell-free system capable of delivering various types of cargo. These vesicles serve as a basis for the design of a targeted multifunctional vehicle for simultaneous imaging and delivery of small molecules or therapeutic proteins.