胃癌血管靶向肽GX1修饰的人血清白蛋白用于胃癌近红外活体成像  

Human Serum Albumin Modified by Gastric Cancer Targeted Peptide-GX1 for Gastric Cancer Near-Infrared Fluorescence Imaging in Vivo

作　　者：李想[1] 殷继鹏[1] 聂勇战[1] 吴开春[1] 王钧[2] 

机构地区：[1]第四军医大学西京消化病医院肿瘤生物学国家重点实验室,陕西西安710032 [2]解放军第451医院消化科,陕西西安710061

出　　处：《现代生物医学进展》2015年第16期3010-3013,3027,共5页Progress in Modern Biomedicine

基　　金：国家自然科学基金重大项目(81090270;81090273);国家973项目(2010CB529302)

摘　　要：目的:以肿瘤血管靶向肽GX1修饰的人血清白蛋白(HSA)作为吲哚菁绿(ICG)的载体,合成近红外荧光探针GX1-HSA-ICG,研究其作为近红外荧光探针在荷人胃癌裸鼠活体中的靶向成像能力。方法:以HSA作为ICG的载体,通过化学修饰与GX1共价连接,合成GX1-HSA-ICG纳米颗粒探针;使用SDS-PAGE对探针合成进行鉴定;采用探针与脐静脉内皮细胞HUVEC以及与肿瘤细胞共培养的脐静脉内皮细胞Co-HUVEC进行结合和竞争抑制试验,验证探针和Co-HUVEC细胞结合的特异性;利用小动物活体成像系统对皮下荷胃癌小鼠进行近红外荧光活体成像,验证探针在体内的胃癌靶向性。结果:成功合成GX1-HSA-ICG。细胞结合与竞争抑制实验显示GX1-HSA-ICG可与Co-HUVEC细胞特异性结合;荷瘤小鼠活体成像也显示出GX1-HSA-ICG较ICG有更长体内的循环时间,并且胃癌组织局部较HSA-ICG有更强的聚集。结论:本研究成功合成了胃癌血管靶向肽GX1修饰的HSA为荧光染料载体的胃癌血管靶向探针,成功对荷胃癌裸鼠进行了活体成像。使用HSA为载体的探针较单纯使用ICG的肿瘤局部滞留能力显著提高,GX1增加了探针的胃癌靶向特异性。该探针在胃癌的早期诊断和抗肿瘤血管生成治疗评估中具有潜在的应用价值。Objective： Here we synthesize a near-infrared fluorescence imaging probe GX1-HSA-ICG based on human serum albumin/indocyanine green functionalized with gastric cancer targeted specific peptide GX1 and evaluate its targeted specificity in vitro and in vivo. Methods： Indocyanine green（ICG） was conjugated to human serum albumin（HSA） by electrostatic and hydrophobic interactions, then GX1 was covalently bond to the HSA-ICG. GX1-HSA-ICG was characterized by SDS-PAGE and Coomassie brilliant blue staining. To evaluate the cancer target specificity and fluorescence imaging capability, GX1-HSA-ICG was incubated with HUVEC and Co-HUVEC cells in vitro and was injected via tail vein of gastric cancer xenograft mice in vivo. Fluorescence intensity was detected by IVIS system. Results： SDS-PAGE and Coomassie brilliant blue staining confirmed the successful synthesis of GX1-HSA-ICG. In vitro assays showed that GX1-HSA-ICG could specifically bind to Co-HUVEC cells and in vivo fluorescence imaging revealed that GX1-HSA-ICG could selectively accumulate to the tumor site of SGC7901 xenograft mice with prolonged circulation time. Conclusions：GX1 could be conjugated to HSA-ICG and GX1-HSA-ICG could targeted specifically to Co-HUVEC in vitro. GX1-HSA-ICG showed a gastric tumor-targeting ability in vivo, and could play a potential role in the diagnosis of gastric cancer and evaluation of therapy response.

关 键 词：GX1 分子影像 胃癌 近红外成像 

分 类 号：R735.2[医药卫生—肿瘤] Q95-3[医药卫生—临床医学]