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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: To synthesize near infrared fluorescent probe GX1-HSA-ICG with human serum albumin (HSA) modified by tumor vascular targeting peptide GX1 as carrier of indocyanine green (ICG) Targeting Imaging Ability of Human Gastric Cancer in Nude Mice. METHODS: GX1-HSA-ICG nanoparticle probes were synthesized by covalently linking HSA to ICG with GX1 by chemical modification. The synthesis of the probes was identified by SDS-PAGE. HUVECs were incubated with HUVECs of umbilical vein endothelial cells The co-cultured human umbilical vein endothelial cells Co-HUVECs were tested for binding and competition inhibition to verify the specificity of the probe binding to Co-HUVEC cells. The mice bearing subcutaneous gastric-cancer were exposed to near-infrared fluorescence using live animal imaging system Imaging, validation probe for gastric targeting in vivo. Results: GX1-HSA-ICG was successfully synthesized. Cell binding and competition inhibition experiments showed that GX1-HSA-ICG could specifically bind to Co-HUVEC cells; in vivo imaging of tumor-bearing mice also showed a longer in vivo circulation time of GX1-HSA-ICG than ICG, and local More aggresome than HSA-ICG. Conclusion: This study successfully synthesized the gastric cancer vascular targeting peptide GX1 modified HSA fluorescent dye carrier for gastric cancer vascular targeting probe, the success of gastric cancer in nude mice imaging. Compared with the ICG alone, the local retention capacity of the HSA-loaded probe was significantly increased, and GX1 increased the specificity of the probe for gastric cancer targeting. The probe has potential application value in the early diagnosis of gastric cancer and the evaluation of antiangiogenic therapy.