Ligand-Targeted Binding of a Novel Silicone Magnetic Microsphere

Abstract

In ligand-targeted drug delivery, a carrier particle conjugated with a ligand binds preferentially to an overexpressed receptor on the membrane of a specific cell type. A therapeutic agent is adsorbed onto or absorbed within the carrier, and its release is often triggered by magnetic stimulation or other means. In this work, we demonstrate ligand-targeted delivery with a novel magnetic microsphere by conjugating the drug carriers with a folic acid ligand that preferentially binds to HeLa cells overexpressing folic acid receptors. The microspheres used in this study are produced in-house and contain magnetite nanoparticles (∼10 nm) distributed uniformly throughout an amine-functionalized silicone matrix. The sphere diameter is scalable from 0.5 to 2.0 microns, and the concentration of magnetic nanoparticles can be varied up to 50% wt. The silicon matrix of this carrier facilitates compatibility with lipophilic drugs, the high magnetic content allows the potential for magnetically-stimulated drug release, and an abundance of primary amines within the matrix enables surface functionalization with a variety of ligands. Microspheres in this study were conjugated with folic acid using an EDAC reaction and tagged with a fluorophore. The spheres were incubated with HeLa cells, which overexpress folate-binding protein, and the degree of binding after 30 minutes was analyzed with fluorescence microscopy. We show a five-fold increase in bound spheres per cell relative to a control sphere without folic acid, indicating a high degree of specific binding. The preferential binding of ligand-conjugated magnetic microspheres gives insight into the utility of these drug carriers for targeted drug delivery studies.