转铁蛋白修饰的载新吲哚菁绿脂质体的制备及其对乳腺癌光动力治疗作用研究  

Preparation of Transferrin Modified IR820 Targeting Liposomes and Its Effect on Photodynamic Therapy of Breast Cancer

作　　者：卢雪 张书贺 赵艺涵 金明姬 高钟镐 金光明 LU Xue;ZHANG Shuhe;ZHAO Yihan;JIN Mingji;GAO Zhonggao;JIN Guangming(Department of Ultrasound,Yanbian University Hospital,Yanji 133000,China;State Key Laboratory of Bioactive Substance and Functions of Natural Medicines,Beijing Key Laboratory of Drug Delivery Technology and Novel Formulations,Institue of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China)

机构地区：[1]延边大学附属医院超声医学科,吉林延吉133000 [2]中国医学科学院北京协和医学院药物研究所,天然药物活性物质与功能国家重点实验室,药物传输技术及新型制剂北京市重点实验室,北京100050

出　　处：《中国药学杂志》2024年第11期1023-1031,共9页Chinese Pharmaceutical Journal

基　　金：吉林省自然科学基金面上项目资助(YDZJ202201ZYTS204)。

摘　　要：目的制备转铁蛋白(Tf)修饰的载光敏剂新吲哚菁绿(IR820)脂质体,并对其进行表征,结合光动力治疗(PDT)乳腺癌4T1细胞及原位乳腺癌小鼠模型,为临床治疗乳腺癌提供一种新思路。方法采用薄膜分散法分别制备载IR820脂质体(IR820@Lipo)和Tf修饰的载IR820脂质体(Tf-IR820@Lipo),采用紫外(UV)法检测其包封率,用透射电子显微镜和粒径仪考察其理化性质;以激光共聚焦和流式细胞技术观察4T1细胞对两者的摄取情况;CCK8实验评价两者对4T1细胞的增殖抑制;活性氧(ROS)检测在激光(Laser)照射下两者细胞内荧光强度差异;体内小动物成像法观察药物在模型小鼠内的聚集情况;体内药效学研究分析药物抗癌作用及毒副作用。结果IR820@Lipo和Tf-IR820@Lipo平均粒径分别为(84.30±15.66)、(116.20±14.68)nm,电位分别为(-8.21±2.06)、(-5.23±1.19)mV;透射电镜表征显示该脂质体呈类球形,分布均匀;IR820@Lipo的包封率为(94.61±0.67)%,载药量为(8.82±0.92)%;Tf-IR820@Lipo的包封率为(95.55±0.83)%,载药量为(8.92±1.01)%。Tf-IR820@Lipo在Laser照射下能显著抑制4T1细胞的增殖并促进其凋亡;ROS检测结果显示Tf-IR820@Lipo在Laser照射下能使4T1细胞内荧光强度明显增强;荷瘤小鼠的体内实验结果显示,Tf-IR820@Lipo光照组在小鼠体内具有较高的肿瘤靶向性;体内药效学研究显示Tf-IR820@Lipo对乳腺癌的抑制作用最强,且未造成小鼠的肝肾功能损伤,无明显的毒副作用。结论Tf-IR820@Lipo以其高靶向性、高疗效及低毒性有望成为治疗乳腺癌的新型制剂。OBJECTIVE To prepare and characterize transferrin(Tf)modified liposomes containing photosensitizing agent indocyanine green(IR820),and to provide a new idea for the clinical treatment of breast cancer by combining photodynamic therapy(PDT)in 4T1 breast cancer cells and the mouse model of breast cancer in situ.METHODS The liposome loaded with IR820(IR820@Lipo)and the Tf modified liposome loaded with IR820(Tf-IR820@Lipo)were prepared by the film dispersion method,respectively.The encapsulation efficiency was detected by UV method,and the physical and chemical properties were investigated by transmission electron microscope and particle size meter.CCK8 assay was used to evaluate the inhibitory effect of the two drugs on the proliferation of 4TI cells.The intracellular fluorescence intensity of the two drugs under laser irradiation was detected by reactive oxygen species(ROS).In vivo pharmacodynamic study was performed to analyze the anticancer effect and toxic side effects of drugs.RESULTS The average particle size of IR820@Lipo and Tf-IR820@Lipo were(84.30±15.66)and(116.20±14.68)nm,respectively,and the Zeta potential were(-8.21±2.06)and(-5.23±1.19)mV,respectively.Transmission electron microscopy showed that the liposome was spherical and uniformly distributed.The encapsulation efficiency of IR820@Lipo was(94.61±0.67)%,and the drug loading was(8.82±0.92)%.The encapsulation efficiency of Tf-IR820@Lipo was(95.55±0.83)%,and the drug loading was(8.92±1.01)%.Tf-IR820@Lipo could significantly inhibit the proliferation and promote the apoptosis of 4T1 cells under laser irradiation.ROS detection results showed that Tf-IR820@Lipo could significantly enhance the fluorescence intensity of 4T1 cells under laser irradiation.The results of in vivo experiments in tumor-bearing mice showed that the Tf-IR820@Lipo light groups had higher tumor targeting in mice.The pharmacodynamic study in vivo showed that Tf-IR820@Lipo had the strongest inhibitory effect on breast cancer,and did not cause liver and kidney function damage in

关 键 词：转铁蛋白光敏性脂质体 光动力疗法 乳腺癌 新吲哚菁绿 

分 类 号：R944.9[医药卫生—药剂学]