低密度脂蛋白配体修饰的阿霉素脂质体的制备及抗肿瘤作用的评价  

Preparation of doxorubicin liposomes modified with low density lipoprotein ligand and evaluation of their anti-tumor effects

作　　者：张泽南 毕晓林 隋忠国[1,4] ZHANG Zenan;BI Xiaolin;SUI Zhongguo(School of Pharmacy,Qingdao University,Qingdao 266021,China;Department of Pharmacy,Affiliated Hospital of Qingdao University,Qingdao 266000,China;Department of Nutrition,Afiliated Hospital of Qingdao University,Qingdao 266000,China;Dean's Office,Affiliated Hospital of Qingdao University,Qingdao 266000,China)

机构地区：[1]青岛大学药学院,山东青岛266021 [2]青岛大学附属医院药学部,山东青岛266000 [3]青岛大学附属医院营养科,山东青岛266000 [4]青岛大学附属医院院长办公室,山东青岛266000

出　　处：《沈阳药科大学学报》2022年第10期1174-1182,共9页Journal of Shenyang Pharmaceutical University

摘　　要：目的 制备低密度脂蛋白配体-ApoB-100蛋白修饰的脂质体,进一步提高阿霉素在体内的靶向性及抗肿瘤效率。方法 采用主动载药方法制备了阳离子阿霉素脂质体(Lipo/DOX),并进一步利用能够结合肿瘤表面高表达的低密度脂蛋白受体的ApoB-100蛋白制备了ApoB蛋白修饰的阿霉素脂质体(ApoB-Lipo/DOX)。结果 该靶向脂质体具有较好的制剂学性质,平均粒径为(138.2±2.3)nm, PDI为0.135±0.06,具有较好的分散性和稳定性。细胞学实验证明空白脂质体对肿瘤细胞没有显著细胞毒性,修饰的阿霉素脂质体能够有效提高阿霉素的细胞摄取效率,增加对肿瘤细胞的抑制效率。体内抗肿瘤实验证明ApoB修饰的脂质体能够增加阿霉素在肿瘤组织的聚集量并有效提高阿霉素的抗肿瘤效果。结论 ApoB-Lipo/DOX能够有效提高阿霉素在体内的靶向性及抗肿瘤效率。Objective To prepare liposomes modified with low density lipoprotein ligand ApoB-100 protein, and to further improve the targeting and anti-tumor efficiency of doxorubicin(DOX) in vivo.Methods In this paper, the cationic DOX liposomes(Lipo/DOX) were prepared by the active loading method, and the ApoB protein modified Lipo/DOX(ApoB-Lipo/DOX) were further prepared by the grafting of ApoB-100 protein which can bind to the high expression low density lipoprotein receptor on the tumor surface.Results The targeted liposomes had good pharmacologic properties, with an average particle size of(138.2±2.3) nm and PDI of 0.135±0.06,showing good dispersity and stability.Cytological experiments showed that blank liposomes had no significant cytotoxicity to tumor cells, and modified DOX liposomes could effectively improve the uptake efficiency of DOX and increase the inhibition efficiency of DOX to tumor cells.In vivo antitumor experiments showed that ApoB-Lipo/DOX can increase the amount of DOX in tumor tissues and effectively improve the antitumor effect of DOX.Conclusion ApoB-Lipo/DOX can effectively improve the targeting and anti-tumor efficiency of DOX in vivo.

关 键 词：ApoB蛋白 脂质体 阿霉素 肿瘤治疗 

分 类 号：R94[医药卫生—药剂学]