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

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

Synthesis and Study of Thermoresponsive Amphiphilic Copolymers via RAFT Polymerization

“…It means that the reactivity ratios of both monomers (r 1 and r 2 ) are lower than unity. There are numerous papers describing synthesis and investigation of block polymers consisting of styrene and PEG methacrylates [37,38] published in the literature; however, there are no publications describing RAFT copolymerization of such monomers. Despite this fact, the free radical polymerization of monomers with a similar structure was extensively studied earlier.…”

Effect of tertiary amino groups in the hydrophobic segment of an amphiphilic block copolymer on zinc phthalocyanine encapsulation and photodynamic activity

“…This can be expected because of the very low ZnPc concentration in comparison to that used in our previous study. 58 In contrast, ZnPc-loaded micelles of 1 exerted excellent photocytotoxicity under the same condition; almost complete annihilation was achieved upon photoirradiation of 20 J cm −2 with a ZnPc dose of only 0.05 μM.…”

“…56,57 Previously, we demonstrated the synthesis of polystyrene-bpoly(polyethylene glycol monomethyl ether acrylate) (PSt-b-PPEGA) and the preparation of ZnPc-loaded polymer micelles. 58 The efficiency of encapsulating ZnPc depended on the molecular architecture of PSt-b-PPEGA. Disappointingly, the photocytotoxicity of the resulting ZnPc-loaded polymer micelles was very low in HeLa cells.…”

Recent Progress in Phthalocyanine-Polymeric Nanoparticle Delivery Systems for Cancer Photodynamic Therapy

“…In this context, Feuser et al [ 66 ] reported ZnPc loaded poly(methyl methacrylate) (PMMA) NPs as PDT agents for leukemia treatment. Obata et al reported a series of polystyrene- b -poly(polyethylene glycol monomethyl ether acrylate) (PSt- b -PPEGA) [ 67 ] and poly(N-substituted acrylamide)- b -poly(polyethylene glycol monomethyl ether acrylate) (P(R)- b -PPEGA) [ 68 ] copolymers synthesized via RAFT as nanocarriers for ZnPc for PDT. Both systems displayed the light-dose-dependent cytotoxicity of ZnPc-loaded micelles in cancer cells, suggesting a promising photodynamic effect for hydrophobic PS loaded in micelles.…”