靶向长循环脂质体造影剂体内外靶向性研究  

Study on tumor targeting ability of neovessel-targeted PEGylated liposomes

作　　者：宋胤[1] 李玮[1] 孟淑燕[1] 唐亮[1] 周蔚[1] 周彩存[1] 

机构地区：[1]同济大学附属肺科医院肿瘤科,上海200433

出　　处：《同济大学学报（医学版）》2011年第2期10-14,共5页Journal of Tongji University(Medical Science)

基　　金：国家"八六三"高技术研究发展计划(2008AA02Z442)

摘　　要：目的通过测定肿瘤新生血管靶向的长循环脂质体造影剂与体外细胞的结合能力及在其体内的代谢、分布情况,研究其对肿瘤的靶向能力。方法薄膜超声法制备包载核磁共振造影剂钆喷酸葡胺注射液(Gd-DTPA)的靶向神经纤毛蛋白-1受体的长循环脂质体造影剂(T-PEG-Gd-LP)和非靶向的长循环脂质体造影剂(NT-PEG-Gd-LP),并观察测定物理性质。实验共设3组,游离组Gd-DTPA、非靶向组NT-PEG-Gd-LP和靶向组T-PEG-Gd-LP,分别测定与人脐静脉内皮细胞(HUVECs)和人肺腺癌细胞(A_(549)cells)的结合能力及注射荷瘤裸鼠模型后的血液和各组织器官中的钆含量。结果靶向组T-PEG-Gd-LP与细胞的结合能力优于其他组别(P<0.05)。与游离组Gd-DTPA相比,NT-PEG-Gd-LP和T-PEG-Gd-LP在血中的清除速率明显减慢,肿瘤、肝、脾、肌肉组织中的药物含量明显增加,心、肺、肾组织中明显降低。与非靶向组NT-PEG-Gd-LP相比,靶向组T-PEG-Gd-LP在肿瘤组织中的药物含量显著增加。结论肿瘤新生血管靶向的长循环脂质体造影剂在体外结合和体内分布情况都表现出良好的肿瘤靶向性。Objective To design and prepare neovessel-targeted PEGylated liposomes and to analyze the tumor targeting ability by evaluating its cell binding capacity in vitro and its metabolism and tissue distribution in vivo.Methods Targeting neuropilin-1 receptor PEGylated Gadopentetate Dimeglumine liposomes（T-PEG-Gd-LP） and non-targeting PEGylated Gadopentetate Dimeglumine liposomes（NT-PEG-Gd -LP）,both containing magnetic resonance ultrasound contrast agent Gd-DTPA,were prepared by thin film dispersion sonication methods and their physical properties were observed.Experiments were conducted and classified into three groups：Gd-DTPA group,NT-PEG-Gd-LP group and T-PEG-Gd-LP group.The binding capacity of these three agents with HUVECs and A_（549） cells were determined.The content of Gd in blood and tissues or organs were also determined after these three agents injected in tumor-bearing nude mice models.Results Binding capacity of T-PEG-Gd-LP with cells was better than other groups（P0.05）.In vivo,compared with Gd-DTPA,the clearance rates of NT-PEG-Gd-LP and T-PEG-Gd-LP decreased significantly in the plasma,and Gd concentrations increased remarkably in tumor,liver,spleen and muscle, but decreased in heart,lung and kidney in mice exposed to NT-PEG-Gd-LP and T-PEG-Gd-LP.Compared with NT-PEG-Gd-LP,T-PEG-Gd-LP significantly increased in tumor.Conclusion Tumor neovessel-targeted PEGylated liposomes demonstrates good tumor targeting properties in vitro and in vivo.

关 键 词：新生血管化 肿瘤 脂质体 神经纤毛蛋白-1 药代动力学 组织分布 

分 类 号：R730.5[医药卫生—肿瘤]