(719d) Development of Antiphagocytic CD47-Tagged Polymeric Prodrug Micelles to Target Alpha(v)Beta(3) Integrin-Bearing Cells

Prodrug 5’-DFUR was used as the initiator in ring-opening polymerization of ε-caprolactone to form hydrophobic 5’-DFUR-polycaprolactone, which was then grafted with hydrophilic cationic polymer (i.e., chitosan or polyethyleneimine) to form amphiphilic copolymers for the preparation of stable micellar nanoparticles. The formed polymeric prodrug micelles were biotinylated via the interaction of biotin-NHS with the amines on cationic polymers. CD47-streptavidin (extracellular domain of self-marker CD47) fusion protein was expressed in lysY/I bacteria and then purified by biotinylated agarose column. Through biotin-streptavidin affinity, CD47 was bound to biotinylated polymeric prodrug micelles and showed antiphagocytic efficacy when CD47-tagged polymeric prodrug micelles exposed to J774A.1 macrophages. Since CD47 is not only an antiphagocytic ligand but also an integrin-associated protein, it can be employed to target integrin α_vβ₃, which is overexpressed on tumor-activated neovascular endothelial cells. In this study, CD47-tagged polymeric prodrug micelles were employed to treat two cells lines - one expressing integrin α_vβ₃ and one without integrin α_vβ₃ expression. Results showed that functionalized polymeric drug nanocarriers were successfully targeted to integrin α_vβ₃ by using CD47 as a targeting moiety.