超声联合载色素上皮源性因子免疫纳米脂质体靶向治疗脉络膜新生血管  

Targeting therapy of pigment epithelium derived factor mediated by ultrasound activated immunoliposome for choroidal neovascularization

作　　者：李涛[1] 韩勇[2] 张虹[1] 徐玲娟[1] 向艳[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院眼科,武汉430030 [2]华中科技大学同济医学院附属协和医院药剂科,武汉430030

出　　处：《眼科研究》2010年第7期586-590,共5页Chinese Ophthalmic Research

基　　金：国家自然科学基金青年科学基金项目(30600691);国家自然科学基金对外交流与合作项目(30811260207)

摘　　要：目的研究超声联合载色素上皮源性因子(PEDF)免疫纳米脂质体对脉络膜新生血管(CNV)的靶向治疗作用。方法以CNV内皮细胞上血管内皮生长因子受体-2(VEGFR-2)为靶向位点,将其配体寡肽连接到纳米脂质体上,再反向装载PEDF,制备能与CNV内皮细胞特异性结合的免疫纳米脂质体。对48只BN大鼠右眼行半导体倍频激光(波长为532nm)光凝术建立CNV模型。光凝后7d,实验组鼠尾静脉分别注射游离PEDF、载PEDF脂质体、载PEDF免疫脂质体,联合眼局部超声波辐照20s,并设立玻璃体腔注射PEDF组和对照组。光凝后14d,脉络膜巩膜冰冻切片观察免疫脂质体对CNV的靶向性。FITC-右旋糖酐标记脉络膜巩膜铺片行新生血管定量分析。结果载PEDF免疫脂质体可特异性靶向结合CNV。CNV与FITC标记的PEDF免疫纳米脂质体结合而呈现绿色荧光,正常脉络膜血管不显现荧光。玻璃体腔注射PEDF组及鼠尾静脉注射游离PEDF、载PEDF脂质体、载PEDF免疫脂质体组CNV面积均较对照组减少,差异有统计学意义(P<0.05)。超声联合PEDF免疫纳米脂质体组对CNV的抑制作用强于玻璃体腔注射PEDF组(P<0.05)。结论动物实验证实PEDF免疫纳米脂质体可特异性结合CNV细胞,超声可增强PEDF免疫纳米脂质体对CNV的抑制作用,该方法有望为眼新生血管的治疗提供新途径。Background Research demonstrated that pigment epithelium derived factor（PEDF） is critical in the inhibition of the treatment of neovascularization.It can selectively destruct the endothelial cells of new blood vessel but without impact to normal vessel.However,the route of administration of PEDF is a key issue in the clinical application of PEDF for treatment of choriodal neovascularization（CNV）.Objective This study was to evaluate the targeting therapy of PEDF mediated by ultrasound activated immunoliposome for CNV.Methods Immunoliposome conjugate was made by conjugating nanoparticle to the poly（ethylene glycol） followed by linkage to the peptide ATWLPPR known to bind the receptor-2 for vascular endothelial growth factor（VEGFR-2）,which is selectively expressed on retinal and choroidal neovascularization.PEDF was reversely loaded into immunoliposomes.Experimental CNV was induced by laser photocoagulation in the right eyes of 48 healthy male Brown Norway rats.PEDF,liposome encapsulating PEDF or immunoliposome encapsulating PEDF was administered via tail vein with ophthalmic ultrasound exposure on days 7.Three normal male Brown Norway rats were as normal control group.On the 14th day after photocoagulation,the rats were sacrificed and the eyes were enucleated and processed for snap-frozen examination.The area of CNV by high molecular weight FITC-dextran for high resolution angiography in choroid-sclera was analyzed by flat mounts.This experiment followed the Standard of Association for Research in Vision and Ophthalmology.Results The immunoliposomes could bind CNV peculiarly,and FITC-PEDF immunoliposome nanoparticles on CNV showed the green fluorescence,and no any fluorescence was seen in normal choroidal vessels.The CNV area was significantly decreased in PEDF intravitreal injection group,PEDF intravitreal injection group,liposome PEDF＋ultrasound group and immunoliposome PEDF＋ ultrasound group in comparison with control group（P0.05）.Immunoliposome encapsulating PEDF＋ultrasound group playe

关 键 词：脉络膜新生血管 色素上皮源性生长因子 超声 纳米 免疫脂质体 

分 类 号：R773[医药卫生—眼科]