c(RGD)2与Angiopep-2共修饰的脂质体的制备、131 I标记与生物分布特征  

The Preparation,131 I Labeling and Bioditribution Evaluation of a Novel DualTargeting Liposome Modified with c(RGD)2 and Angiopep-2

作　　者：王玉琦 仰浈臻[2,3] 申镐源 杜祎甜[2] 崔永刚 李嘉嘉 郭凤琴[1] 王荣福 齐宪荣[2] 张春丽[1] WANG Yuqi;YANG Zhenzhen;SHEN Haoyuan;DU Yitan;CUI Yonggang;LI Jiajia;GUO Fengqin;WANG Rongfu;QI Xianrong;ZHANG Chunli(Department of Nuclear Medicine,Peking University First Hospital,Beijing 100034,China;School of Pharmacy,Peking University,Beijing 100083,China;Drug Clinical Trial Center,Peking University Third Hospital,Beijing 100089,China;Qingdao Hospital of Rehabilitation University,Qingdao Municipal Hospital,Qingdao 266011,China)

机构地区：[1]北京大学第一医院核医学科,北京100034 [2]北京大学药学院,北京100083 [3]北京大学第三医院药物临床试验机构,北京100089 [4]康复大学青岛医院(青岛市市立医院),山东青岛266011

出　　处：《标记免疫分析与临床》2023年第5期851-856,共6页Labeled Immunoassays and Clinical Medicine

基　　金：北京市自然科学基金(编号:7212211);北京大学医学科技创新平台发展基金-医学交叉种子基金资助项目(编号:BMU2018MX009)。

摘　　要：目的为制备具有穿透血脑屏障和血脑肿瘤屏障能力及靶向脑胶质瘤的脂质体载体,合成以靶向肿瘤新生血管的c(RGD)2肽与脑靶向肽Angiopep-2共修饰的脂质体,用131 I标记并研究其生物分布特征。方法将c(RGD)2与Angiopep-2分别与DSPE-PEG2000偶联,用氢化大豆磷脂、胆固醇、DSPE-PEG2000-Angiopep-2和DSPE-PEG2000-c(RGD)2按摩尔比为60∶34∶3∶3制备脂质体,采用氯胺T法进行131 I标记,测定131 I标记的c(RGD)2与Angiopep-2共修饰的脂质体在小鼠体内的生物分布。结果所合成的DSPE-PEG2000-Angiopep-2与DSPE-PEG2000-c(RGD)2经质谱测定的分子量与理论值相符;c(RGD)2与Angiopep-2共修饰的脂质体的平均粒径为143.2±13.8nm,多分散系数(PDI)为0.214±0.039,Zeta电位为-13.00±1.95;131 I标记率为87.57%±3.00%,经分离纯化后放射化学纯度为90.98%±1.69%;131 I标记的c(RGD)2与Angiopep-2共修饰的脂质体在小鼠肝、脾、胃、肾有较高的摄取,尾静脉注射后1h与3h脑摄取率分别为(0.08±0.02)%ID/g与(0.13±0.03)%ID/g。结论成功制备了一种新型的以Angiopep-2和c(RGD)2修饰的脂质体,并探讨了其生物分布特征。其对脑胶质瘤的体内靶向作用有待于进一步研究。Objective To obtain the liposome carrier that can penetrate blood-brain barrier(BBB)and blood-brain tumor barrier(BBTB)and target to glioma.A dual-targeting liposome modified with tumor angiogenesis targeting peptide c(RGD)2 and brain-targeting peptide Angiopep-2 was prepared,labeled with 131 I and the biodistribution.The evaluation study was then conducted.Methods c(RGD)2 and Angiopep-2 were conjugated to DSPE-PEG2000,respectively.The liposome was prepared with the formulation of hydrogenated soybean phosphatidylcholine(HSPC):cholesterol:DSPE-PEG2000-Angiopep-2:DSPE-PEG2000-c(RGD)2 of 60∶34∶3∶3(molar ratio).131 I was labeled with ChT method.The biodistribution of the labeled liposome in mice was measured.Results The molecular weight of DSPE-PEG2000-Angiopep-2 and DSPE-PEG2000-c(RGD)2 measured by mass spectrum was consistent with the theoretical value.The average particle size of the liposome was 143.2±13.8 nm,while the polydispersity index(PDI)was 0.214±0.039 and zeta potential was-13.00±1.95.The radiolabeling yield with 131 I was 87.57%±3.00%and radiochemical purity after purification was 90.98%±1.69%.The uptake of the 131 I labeled liposome in mice was higher in liver,spleen,stomach and kidney.The brain uptake at 4 h and 3 h postinjection was(0.08±0.02)%ID/g and(0.13±0.03)%ID/g,respectively.Conclusion A novel liposome modified with Angiopep-2 and c(RGD)2 was prepared successfully and its biodistribution was measured.The in vivo targeting capability to glioma of the liposome is needed to be further studied.

关 键 词：脂质体 131 I标记 生物分布 脑胶质瘤 

分 类 号：R739.41[医药卫生—肿瘤]