(504a) Quantifying Interactions Between Drug Delivery Vehicles and Target Cells Using An Affinity- and Size-Tunable Model System

Drug delivery vehicles come in all shapes and sizes. We describe micron-length cylindrically shaped vehicles that have high affinity for malignant B-lymphocytes derived from mice. These long cylinders have unique flow properties in the vasculature of rodents, where they remain in the blood (and other areas) for up to one week. This presence in the blood, involving many passes through the spleen (and possibly lymph nodes), encouraged us to use the cylinders to help treat white blood cell cancers. We conjugated A20.1 peptide, which has nanomolar affinity for malignant B-lymphocytes, to the exteriors of the cylinders (A20.1-cylinders) using established poly(ethylene-oxide)-modifying chemistry. We loaded the A20.1-cylinders with the lipophilic membrane dye PKH26 and quantified the fluorescent signal of the cells after incubation with these cylinders. Malignant B-lymphocytes showed an A20.1 concentration-dependent increase in fluorescence. Splenocytes obtained from healthy mice have negligible fluorescent intensity when incubated with the PKH26-loaded A20.1-cylinders. Thus, our system is specific for target cells in vitro. Free A20.1 peptide can compete off the A20.1-cylinders, therefore the binding mechanism seems to be via the A20.1 receptor. Cylinders with lengths less than 2 microns or greater than 10 microns have the highest affinities for the cells. We will use this system to understand the interactions between drug delivery vehicles of varying lengths (sizes) and suspension cells.