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

Makoto Obata; Eika Ishihara; Shiho Hirohara

doi:10.1039/d2ra02224a

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

RSC Adv. 2022 Jun 21;12(28):18144-18153. doi: 10.1039/d2ra02224a. eCollection 2022 Jun 14.

Authors

Makoto Obata¹, Eika Ishihara¹, Shiho Hirohara²

Affiliations

¹ Graduate Faculty of Interdisciplinary Research, University of Yamanashi 4-4-37 Takeda Kofu 400-8510 Japan mobata@yamanashi.ac.jp +81 55 220 8549 +81 55 220 8549.
² Department of Chemical and Biological Engineering, National Institute of Technology, Ube College 2-14-1 Tokiwadai Ube 755-8555 Japan.

Abstract

Polymer micelles are promising nanocarriers for hydrophobic photosensitizers of photodynamic therapy (PDT). Poly(styrene-co-(2-(N,N-dimethylamino)ethyl acrylate))-block-poly(polyethylene glycol monomethyl ether acrylate) (P(St-co-DMAEA)-b-PPEGA; 1) was prepared via reversible addition and fragmentation chain transfer (RAFT) polymerization as a carrier for a zinc phthalocyanine (ZnPc) photosensitizer to be used in PDT. The DMAEA-unit composition in the P(St-co-DMAEA) segment was adjusted to 0.40 molar ratio, which caused a sharp increase in water-solubility when the pH decreased from 7.4 to 5.0. The polymer 1 micelle size distribution also shifted to lower when the pH decreased, whereas this change was not observed in PSt-co-PPEGA (2), which was previously reported. The UV-vis spectrum of the ZnPc-loaded micelles of polymer 1 exhibited relatively sharp Q bands, comparable to those measured in DMSO, indicating good compatibility of the condensed core with ZnPc. ZnPc-loaded micelles of polymer 1 exerted excellent photocytotoxicity in the MNNG-induced mutant of the rat murine RGM-1 gastric epithelial cell line (RGK-1). In contrast, the ZnPc-loaded micelles of polymer 2 were completely inactive under the same conditions. Fluorescence from the RGK-1 cells treated with ZnPc-loaded micelles of polymer 1 was observed after 4 h of co-incubation, while no fluorescence was observed in cells treated with ZnPc-loaded micelles of polymer 2. These results indicate that the pH-responsive nature and good compatibility with ZnPc exhibited by the polymer 1 micelles are essential characteristics of ZnPc carriers for efficient photodynamic therapy.