Article Summary
李想 殷继鹏 聂勇战 吴开春 王钧.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[J].现代生物医学进展英文版,2015,15(16):3010-3013.
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 SerumAlbumin Modified by Gastric Cancer Targeted Peptide-GX1for Gastric Cancer Near-Infrared Fluorescence Imaging in Vivo
  
DOI:
中文关键词: GX1  分子影像  胃癌  近红外成像
英文关键词: GX1 peptide  Molecular imaging  Gastric cancer  Near-Infrared fluorescence imaging
基金项目:国家自然科学基金重大项目(81090270;81090273);国家973项目(2010CB529302)
Author NameAffiliation
李想 殷继鹏 聂勇战 吴开春 王钧 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解放军第451医院消化科 
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中文摘要:
      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。
英文摘要:
      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.Conclusion: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.
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