肿瘤微环境响应的仿生金属纳米粒用于光动力学治疗的研究  

Tumor microenvironment responsive biomimetic nanoparticles for photodynamic tumor therapy

作　　者：郑蓉蓉 赵林平 陈华清 李仕颖 余细勇 ZHENG Rong-rong;ZHAO Lin-ping;CHEN Hua-qing;LI Shi-ying;YU Xi-yong(Guangdong Key Laboratory of Molecular Target and Clinical Pharmacology,State Key Laboratory of Respiratory Diseases Pharmacology Group,School of Pharmaceutical Sciences of Guangzhou Medical University,Guangzhou 511436,China)

机构地区：[1]广州医科大学药学院,广东省分子靶标与临床药理学重点实验室,呼吸疾病国家重点实验室药理学组,广东广州511436

出　　处：《药学学报》2020年第7期1672-1679,共8页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金-广东联合基金重点项目(U1601227);广东省科技计划重大专项(2015B020225006)。

摘　　要：本文基于生物配位化合物和仿生金属蛋白的概念,将组氨酸修饰的光敏剂功能化序列与锌离子配位,形成仿生金属纳米粒(nanoparticles,NPs)。NPs在高谷胱甘肽(glutathione,GSH)和低pH值的肿瘤微环境条件下可被降解释放,进而实现肿瘤光动力学治疗。通过检测NPs的粒径、电势、紫外吸收和荧光吸收对其进行结构性质表征,应用单线态氧绿色荧光探针(single oxygen sensor green,SOSG)试剂盒检测NPs体外单线态氧的产生,以小鼠乳腺癌细胞4T1为研究对象,考察NPs的亚细胞器分布和细胞毒性等。研究结果表明,NPs具有良好的分散性和稳定性,结构均一,粒径约为165 nm,具有肿瘤微环境响应性,能有效抑制4T1细胞活性,诱导细胞凋亡。本研究表明,基于组氨酸和锌离子配位的仿生纳米药物具有良好的生物相容性和小鼠乳腺癌细胞毒性,该组装配位策略可为开发新型智能纳米药物带来新思考。Inspired by the coordination effects between imidazole and metal ions in hemoglobin,biomimetic nanoparticles were constructed for photodynamic tumor therapy.The photosensitizer of protoporphyrin IX(PpIX)was modified with histidine,which could be self-assembled with Zn2+to obtain the biomimetic nanoparticles(NPs).Under the conditions of high glutathione and low pH,the biomimetic nanoparticles could be degraded and released for enhanced photodynamic tumor therapy.The structures of NPs were characterized by dynamic light scattering(DLS),UV-visible spectrophotometer(UV-Vis),fluorescence microscope and transmission electron microscope(TEM).The reactive oxygen species(ROS)production ability of NPs was measured by singlet oxygen sensor green(SOSG)test kit.Mouse breast cancer cell lines(4T1 cells)were employed to investigate the subcellular organelle distribution and cytotoxicity of NPs.These results confirmed that NPs possessed a good dispersibility and stability with a uniform structure and particle size at 165 nm.Moreover,MTT assay and live/dead cell staining assay demonstrated that NPs could inhibit the proliferation of 4T1 cells and exhibit a good biocompatability.This research would promote the construction of intelligent biomedicine for tumor precision therapy.

关 键 词：组氨酸 锌离子 纳米药物 配位效应 肿瘤微环境 光动力学治疗 

分 类 号：R943[医药卫生—药剂学]