A novel approach to synthesize polymers for potential photodynamic therapy: from benzenedinitrile to phthalocyanine

Abstract

Benzenedinitrile, a precursor for the synthesis of phthalocyanine, was incorporated into a methacrylate monomer, 2-methyl-acrylic acid 6-(3,4-dicyano-phenoxy)-hexyl ester (MADCE). The benzenedinitrile monomer was homo-polymerized, chain-extended and copolymerized with oligo(ethylene glycol) methyl methacrylate (OEGMEMA) via the reversible addition–fragmentation chain transfer (RAFT) method. The resulting homopolymer, block and random copolymers obtained were used to synthesize polymers with Zn(II)phthalocyanine (ZnPc) side-chains by reacting with excess benzenedinitrile derivatives, 4-(octyloxy)phthalonitrile (OPN). GPC, FTIR, UV-Vis, NMR, fluorescence, and atomic absorption spectroscopy were used to characterize the Zn(II)phthalocyanine-functionalized polymers. The ZnPc-functionalized polymers generate singlet oxygen species with good quantum yields, which are believed to be the major cytotoxic reactive oxygen species (ROS) for photodynamic therapy. Among them, copolymers present enhanced singlet oxygen quantum yields (Φ_Δ = 0.49 and 0.40 in DMF, Φ_Δ = 0.68 and 0.73 in aqueous media) compared to the homopolymer (Φ_Δ = 0.28). The ZnPc-functionalized copolymers self-assembled into nanoparticles in aqueous solutions, which was confirmed by DLS and TEM, and the nanoparticles show good stability in the presence of salt and proteins. This novel and efficient method of synthesizing water-soluble ZnPc-functionalized polymers with good singlet oxygen quantum yields provides a simple approach to fabricate polymeric materials for photodynamic therapy.