【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¹³¹I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¹³¹I标记，测定¹³¹I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;¹³¹I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%;¹³¹I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。更多还原

【Abstract】 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 ¹³¹I 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）. ¹³¹I 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 ¹³¹I was 87.57%±3.00% and radiochemical purity after purification was 90.98%±1.69%. The uptake of the ¹³¹I 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.更多还原