Effect of the hydrophobic segment of an amphiphilic block copolymer on micelle formation, zinc phthalocyanine loading, and photodynamic activity

Abstract A series of amphiphilic block copolymers, i.e., poly(N-substituted acrylamide)-block-poly(polyethylene glycol monomethyl ether acrylate) (P(R)-b-PPEGA) were prepared via RAFT polymerization and post-polymerization modification, and the formation of polymeric micelles as zinc(II) phthalocyanine (ZnPc) carriers for photodynamic therapy was investigated. The effect of hydrophobic R groups at the hydrophobic segment of the block copolymer on critical micelle concentration, hydrodynamic diameters ZnPc-loading ability, and in vitro photocytotoxicity of the polymer micelles was examined. The hydrodynamic diameters of the polymer micelles were insensitive to R groups and falls in a narrow range between 23 to 25 nm, whereas those of the ZnPc-loaded micelles vary from 167 to 230 nm depending on the R groups. The Q bands in UV-vis spectra of the ZnPc-loaded micelles indicate that the presence of aromatic R groups results in loose ZnPc aggregates, whereas those containing aliphatic R groups are well packed. The photodynamic effect examined in RGK-1 cell lines was also dependent on the R groups; ZnPc-loaded micelles having aromatic R groups exert higher photodynamic effect than those with aliphatic R groups. These findings indicate that aromatic R groups form larger polymeric micelles with loosely packed ZnPc aggregates, leading to enhanced release of ZnPc in cellular environment and therefore higher photodynamic effect.