Zinc phthalocyanine encapsulated in polymer micelles as a potent photosensitizer for the photodynamic therapy of osteosarcoma

Wei Yu; Mingzhou Ye; Jian Zhu; Yitian Wang; Chengzhen Liang; Jianbin Tang; Huimin Tao; Youqing Shen

doi:10.1016/j.nano.2018.02.005

Zinc phthalocyanine encapsulated in polymer micelles as a potent photosensitizer for the photodynamic therapy of osteosarcoma

Nanomedicine. 2018 Jun;14(4):1099-1110. doi: 10.1016/j.nano.2018.02.005. Epub 2018 Feb 17.

Authors

Wei Yu¹, Mingzhou Ye², Jian Zhu¹, Yitian Wang¹, Chengzhen Liang¹, Jianbin Tang³, Huimin Tao⁴, Youqing Shen²

Affiliations

¹ Department of Orthopedics, the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China; Orthopedics Research Institute of Zhejiang University, Hangzhou, China.
² Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Center for Bionanoengineering, and College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, China.
³ Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Center for Bionanoengineering, and College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, China. Electronic address: jianbin@zju.edu.cn.
⁴ Department of Orthopedics, the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China; Orthopedics Research Institute of Zhejiang University, Hangzhou, China. Electronic address: 2187040@zju.edu.cn.

PMID: 29462663
DOI: 10.1016/j.nano.2018.02.005

Abstract

Zinc phthalocyanine (ZnPc) is a highly potent second-generation photosensitizer for cancer photodynamic therapy (PDT) with attractive photo-physical and photo-chemical properties. However, poor solubility and strong trend of crystallization prevent it from loading in most of drug delivery systems and hamper its further application. Herein, to overcome this problem, an amphiphilic block copolymer poly(ethylene glycol)-poly[2-(methylacryloyl)ethylnicotinate] (PEG-PMAN) with aromatic nicotinate is used to load ZnPc for their π-π interactions. The formed PEG-PMAN/ZnPc nanoparticle (PPZ) dramatically increases reactive oxygen species production in osteosarcoma cells after light irradiation, causes mitochondrial injury and promotes cell cycle arrest at G2/M, leading to a 100-fold cytotoxicity improvement comparing with free ZnPc. The excellent therapeutic effectiveness and safety of PPZ are also proved by in vivo experiments operating on osteosarcoma model. The finding above indicates that PPZ has promising clinical applications as a next-generation photosensitizer in PDT of osteosarcoma.

Keywords: Nanoparticles; Osteosarcoma; Photodynamic therapy; Polymer micelle; Zinc phthalocyanine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line, Tumor
Humans
Indoles / chemistry*
Isoindoles
Membrane Potential, Mitochondrial / drug effects
Mice
Micelles
Nanoparticles / chemistry
Organometallic Compounds / chemistry*
Osteosarcoma / therapy*
Photochemotherapy / methods*
Photosensitizing Agents / chemistry*
Polymers / chemistry*
Zinc Compounds

Substances

Indoles
Isoindoles
Micelles
Organometallic Compounds
Photosensitizing Agents
Polymers
Zinc Compounds
Zn(II)-phthalocyanine