基于表面光化学反应偶联多种药物分子制备磁性粒子靶点“钓钩”研究  

Multiple target fishing hook prepared by photochemically coupling molecules in medicines onto magnetic nanoparticles

作　　者：汪火成 郝苏敏 刘瑜琦 郑晓曼[2] 姚璐 刘莲英[1] 曾克武[3] WANG Huo-cheng;HAO Su-min;LIU Yu-qi;ZHENG Xiao-man;YAO Lu;LIU Lian-ying;ZENG Ke-wu(College of Materials Science and Engineering,Beijing University of Chemical Technology,Beijing 100029,China;Beijing Work Station,Technology Center,Shanghai Tobacco Group Co.,Ltd.,Beijing 101121,China;State Key Laboratory of Natural and Biomimetic Drugs,School of Pharmaceutical Sciences,Peking University,Beijing 100191,China)

机构地区：[1]北京化工大学材料科学与工程学院,北京100029 [2]上海烟草集团有限责任公司技术中心北京工作站,北京101121 [3]北京大学药学院,天然药物及仿生药物国家重点实验室,北京100191

出　　处：《中草药》2020年第16期4142-4150,共9页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(81773932)。

摘　　要：目的制备表面接枝含二苯甲酮(BP)聚合物的磁性纳米粒子,并通过BP基团的光化学反应偶联各种药物分子,获得多成分靶点"钓钩"。方法水热法制备表面含羧基磁性纳米粒子(Fe_3O_4-COOH),通过置换获得表面含巯基(-SH)磁性纳米粒子(Fe_3O_4-SH),考察不同置换时间所得粒子表面-SH含量;通过接枝聚合向磁性粒子表面引入含BP基团的聚合物,研究接枝聚合单体配比和用量对BP基团含量的影响;扫描电子显微镜(SEM)观察粒子形貌,傅里叶变换红外光谱仪(FT-IR)和X射线光电子能谱技术(XPS)分析粒子表面组分,热失重(Tg)法测定粒子表面成分含量;紫外(UV)光照下偶联键接不同药物分子,采用聚合物降解、脱除药物方法及光照前后上清液含量测试方法确定磁性粒子表面偶联药物分子含量。结果制备了平均粒径约100 nm的Fe_3O_4-COOH粒子,置换时间延长,表面-SH含量增加;提高接枝聚合反应中含BP基团单体的比例和用量,粒子表面BP基团含量增加;优选分散性好、表面BP基团含量较高的粒子,利用BP基团光化学反应偶联不同药物分子,FT-IR、紫外-可见光分光光度计(UV-Vis)测试分析证实了药物分子的偶联和选择性。结论为制备中药成分芯片并用于中药靶点群"钩钓"提供了有效方法和依据。Objective To achieve multiple target fishing hook by efficiently grafting polymers containing benzophenone(BP) groups and photochemically coupling molecules in medicines onto magnetic nanoparticles(MNPs). Methods MNPs attached carbonyl groups(Fe3O4-COOH) were prepared through a hydrothermal process. Then they were modified with DMSA, forming MNPs with thiol groups(Fe3O4-SH). Fe3O4-SH nanoparticles were grafted with polymer containing BP groups by surface-initiated condensation polymerization. Effects of monomer feed ratios and contents on the amounts of BP groups were investigated. The molecules in medicines were covalently coupled onto MNPs via photochemical reactions of BP groups. The contents of coupled molecules were determined by FT-IR and UV-Vis spectra analyses. Results MNPs with average size of 100 nm were produced, modified with DMSA, and decorated by grafting polymer containing photosensitive BP groups. When the content of monomer containing BP groups was increased in grafting polymerizations, more BP groups were incorporated onto MNPs. This was conductive to the subsequent photocoupling. FT-IR and UV-Vis spectra analyses confirmed the coupling of molecules in medicines. The active H and steric hinderance of the molecules affected their coupling. Conclusion The resultant magnetic target fishing hook is ready as a probe for targets identification of traditional Chinese medicine(TCM).

关 键 词：二苯甲酮 表面接枝改性 药物分子偶联 靶点“钓钩” 聚合物 磁性纳米粒子 光化学反应 水热法 

分 类 号：R283.6[医药卫生—中药学]