邓静泽;黄明东;陈卓;张明鑫;陈锦灿;李林森;
DENG Jingze;HUANG Mingdong;CHEN Zhuo;ZHANG Mingxin;CHEN Jincan;LI Linsen;College of Basic Medical Sciences,Shenyang Medical College;State Key Laboratory of Structural Chemistry,Fujian Institute of Research on the Structure of Matter,Chinese Academy of Sciences;School of Pharmacy,Shenyang Pharmaceutical University;

• 1:沈阳医学院基础医学院
• 2:中国科学院福建物质结构研究所结构化学国家重点实验室
• 3:沈阳药科大学药学院

摘要(Abstract)：

目的合成寡聚赖氨酸酞菁锌(ZnPc-(Lys)9)改善酞菁锌(zinc phthalocyanine,ZnPc)的水溶性,考察ZnPc-(Lys)9对Hep G2细胞的光动力(photodynamic therapy,PDT)杀伤作用,探讨细胞动态分析(electric cell-substrate impedance sensing,ECIS)在PDT研究中的应用。方法采用时间依赖和浓度依赖的方式考察Hep G2对ZnPc-(Lys)9的摄取;利用AlamarBlueTM法和ECIS两种方法检测ZnPc-(Lys)9对Hep G2细胞的杀伤作用。结果合成的ZnPc-(Lys)9具有很好的水溶性且对Hep G2细胞具有明显的光动力学作用; Hep G2对ZnPc-(Lys)9的摄取量随时间和浓度增加而增加; AlamarBlueTM法和ECIS两种方法都证明了ZnPc-(Lys)9对Hep G2细胞有强杀伤作用; ECIS可以实时监测PDT过程中细胞形态学的变化。结论 ZnPc-(Lys)9改善了ZnPc的水溶性且对Hep G2细胞有很好的杀伤作用; ECIS在PDT研究中具有广泛的应用前景。
Objective To synthesize derivative of zinc phthalocyanine( ZnPc) with oligolysine for improving the water solubility of ZnPc. The phototoxicity and dark toxicity of ZnPc-( Lys)9 on HepG2 cells were investigated and the potential applications of electric cell-substrate impedance sensing( ECIS) in PDT were also evaluated. Methods Time-dependent and dose-dependent cellular uptake of ZnPc-( Lys)9 were tested to investigate the uptake value of ZnPc-( Lys)9 in HepG2 cells. The effect of ZnPc-( Lys)9 on HepG2 was determined by AlamarBlueTMtest and ECIS method,respectively. Results The oligolysine-zinc phthalocyanine derivative was highly water soluble,and showed significant photodynamic efficacy on HepG2 cells in vitro. The cellular uptake of ZnPc-( Lys)9 in HepG2 cells increased with the elongation of drug exposure time and concentration. The toxicity results obtained by AlamarBlueTMtest was in accordance with that by ECIS methods. And the changes of the cellar morphologies after PDT could be real-time monitored by the ECIS method. Conclusion ZnPc-( Lys)9 can be used as a good water soluble photosensitizer in PDT,and has higher phototoxicity and lower dark toxicity towards HepG2 cells. ECIS-based phototoxicity assay is a powerful technique to evaluate the photodynamic efficacy of photosensitizers.

关键词(KeyWords)： 光动力治疗;寡聚赖氨酸酞菁锌;抗肿瘤;细胞动态分析
photodynamic therapy;oligolysine-zinc phthalocyanine;anti-cancer;electric cell-substrate impedance sensing

Abstract:

Keywords:

基金项目(Foundation): 辽宁省自然科学基金(20170540875);; 沈阳医学院博士科研启动基金(20143058);沈阳医学院大学生科研立项(20179007);; 沈阳药科大学大学生创新创业训练计划(201710163000051)基金资助项目

作者(Authors): 邓静泽;黄明东;陈卓;张明鑫;陈锦灿;李林森;
DENG Jingze;HUANG Mingdong;CHEN Zhuo;ZHANG Mingxin;CHEN Jincan;LI Linsen;College of Basic Medical Sciences,Shenyang Medical College;State Key Laboratory of Structural Chemistry,Fujian Institute of Research on the Structure of Matter,Chinese Academy of Sciences;School of Pharmacy,Shenyang Pharmaceutical University;

DOI: 10.14066/j.cnki.cn21-1349/r.2018.11.005

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