RAFT synthesis of polystyrene-block-poly(polyethylene glycol monomethyl ether acrylate) for zinc phthalocyanine-loaded polymeric micelles as photodynamic therapy photosensitizers

Makoto Obata, Shuto Tanaka, Hiroshi Mizukoshi, Eika Ishihara, Masaki Takahashi, Shiho Hirohara

Index: 10.1002/pola.28929

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Abstract

ABSTRACT A series of polystyrene-block-poly(polyethylene glycol monomethyl ether acrylate) (PStm-b-PPEGAn) polymers were systematically synthesized as carriers for zinc phthalocyanine (ZnPc) for photodynamic therapy via reversible addition and fragmentation chain transfer polymerization. The degree of polymerization of the styrene (m) and PEGA units (n) of the resulting block copolymers were characterized to be n = 174, 40, and 18 for m = 52; and n = 200, 84, and 31 for m = 30. All the block copolymers formed micelles in water. The critical micelle concentration (CMC) of the PStm-b-PPEGAn was determined by fluorometry using pyrene as a hydrophobic probe. The CMC value increased from 4.5 to 20 mg·L−1 with an increase in the mole fraction of PEGA units. The median diameters of the micelles increased from 19 to 31 nm for PSt52-b-PPEGAn and from 15 to 23 nm for PSt30-b-PPEGAn with increasing n value. ZnPc-loaded micelles were prepared by dialysis of the block copolymer in the presence of ZnPc followed by removal of large aggregates by filtration. The encapsulation efficiency was dramatically changed in the range of 0–68%. The light-dose-dependent cytotoxicity of the ZnPc-loaded PSt30-b-PPEGA200 was clearly established in HeLa cell lines; while no cytotoxicity was confirmed under the dark. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 560–570 A series of polystyrene-block-poly(polyethylene glycol monomethyl ether acrylate) (PStm-b-PPEGAn) were systematically synthesized via RAFT polymerization for a carrier of ZnPc used in photodynamic therapy. Encapsulation efficiency of ZnPc in the block copolymer micelles was dramatically changed with changing the degree of polymerization of PPEGA segments. The light-dose-dependent photocytotoxicity of ZnPc-loaded block copolymer micelles was established in HeLa cell lines.