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 |
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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) |
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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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