Page 21 - 2019年10月第30卷第20期

·药学研究·

基于TiO2@Fe3O4纳米材料的盐酸阿霉素磁性热敏脂质体制备及

其理化特性、磁效应和光热效应考察 Δ

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祝侠丽 ，张慧娟 ，王莎莎 ，李玲华 ，贾永艳（1.河南中医药大学药学院，郑州 450046；2.郑州大学药学院，郑
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1＊
州 450001）
中图分类号 R943 文献标志码 A 文章编号 1001-0408（2019）20-2752-06
DOI 10.6039/j.issn.1001-0408.2019.20.04

摘 要 目的：制备一种包载盐酸阿霉素（DOX）的磁性热敏脂质体（MTSL），考察其理化性质、磁效应和光热效应，为肿瘤的化疗
及光热/光动力治疗提供基础。方法：以DOX为模型药物，以纳米二氧化钛-纳米四氧化三铁复合材料（TiO2@Fe3O4 ）作为光敏剂和
磁性材料，采用薄膜分散法制备DOX-TiO2@Fe3O4-MTSL。观察该脂质体的形态和分散性、粒径及Zeta电位，采用超滤-离心法结
合高效液相色谱法考察其包封率；采用磁强针考察其顺磁性。与DOX溶液比较，采用透析法考察该脂质体的体外释放行为，并比
较在不同温度（37、43 ℃）下的释放曲线。采用808 nm近红外激光照射，考察该脂质体的光热转换效应以及对人乳腺癌MCF-7细
胞中活性氧（ROS）产生的影响。结果：制备的DOX-TiO2@Fe3O4-MTSL为棕黑色，水分散性好；电镜下呈类圆球形，大小较均匀；
平均粒径为250.6 nm，多分散性指数为0.107，Zeta电位为（－7.76±3.41）mV；包封率为（92.3±3.2）％；在外加磁场下可定向移动，
具有明显的顺磁性。与DOX溶液比较，该脂质体释药速度较慢，具有明显的缓释特性；与37 ℃条件比较，该脂质体在43 ℃条件
下的释药速度明显加快。随激光（808 nm）照射时间的增加，该脂质体的温度持续升高，具有明显的光热转换效应，并可使MCF-7
细胞中ROS的产生明显增加。结论：成功制备了DOX-TiO2@Fe3O4-MTSL，其外观形态均匀、理化性质良好；具有明显的顺磁性、
缓释作用和光热转换性能，能在808 nm近红外激光照射下增加MCF-7细胞中ROS的含量。
关键词 纳米二氧化钛；纳米四氧化三铁；TiO2@Fe3O4复合纳米材料；磁性热敏脂质体；盐酸阿霉素；光热治疗；光动力治疗；光热
效应；磁靶向性

Preparation of Adriamycin Hydrochloride Magnetic Thermosensitive Liposome Based on TiO2@Fe3O4 and
Its Physicochemical Properties，Magnetic Effect and Photothermal Effect Study
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ZHU Xiali ，ZHANG Huijuan ，WANG Shasha ，LI Linghua ，JIA Yongyan （1. School of Pharmacy，Henan
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University of TCM，Zhengzhou 450046，China；2. School of Pharmacy，Zhengzhou University，Zhengzhou
450001，China）
ABSTRACT OBJECTIVE： To prepare Adriamycin hydrochloride （DOX） magnetic thermosensitive liposome （MTSL），
investigate its physicochemical properties，magnetic effect and photothermal effect，so as to provide reference for tumor chemo-
therapy and photodynamic/photothermal therapy. METHODS：Using DOX as model drug，TiO2@Fe3O4 as photosensitizers and
magnetic materials，DOX-TiO2@Fe3O4-MTSL was prepared with membrane dispersion method. The morphology and dispersibility
were observed；particle size and Zeta potential were detected；encapsulation efficiency of the liposome were determined by
centrifugal ultrafiltration and HPLC. Its paramagnetism property was also detected by magnetometer. Compared with DOX solution，
in vitro release behavior of the liposome was investigated by dialysis method，and the release curves at different temperatures（at
37，43 ℃）were compared. The photothermal conversion effect of the liposome and the production of reactive oxygen species
（ROS）in human breast cancer MCF-7 cells were investigated by near infrared laser irradiation at 808 nm. RESULTS：Prepared
DOX-TiO2@Fe3O4-MTSL was brown-black with good water dispersion，and was spherical in shape and uniform in size under
electron microscopy. Average particle size was 250.6 nm；polydispersity index was 0.107；Zeta potential was（－7.76±3.41）mV；
encapsulation efficiency was（92.3±3.2）％. Under the external magnetic field，the liposome could move in a directional direction
and had obvious paramagnetism. Compared with DOX solution，the liposomes released slowly and showed obvious sustained-
release characteristics. Compared with at 37 ℃，the drug release of liposome speeded up significantly at 43 ℃.With the increase of
laser（808 nm）irradiation time，the temperature of the liposome kept rising，which had obvious photothermal conversion effect and
could induce the increase of ROS in MCF-7 cells.
Δ 基金项目：国家自然科学基金资助项目（No.81803740）；河南省
CONCLUSIONS：DOX-TiO2@Fe3O4-MTSL is prepared succe-
高等学校青年骨干教师培养计划（No.2016GGJS-081）
ssfully，which has uniform appearance，good physical and
＊副教授，硕士生导师，博士。研究方向：药物新剂型与新技术。
电话：0371-65962746。E-mail：zhuxiali1980@126.com chemical properties. It has obvious paramagnetism sustained

·2752 · China Pharmacy 2019 Vol. 30 No. 20 中国药房 2019年第30卷第20期