[关键词]
[摘要]
目的: 制备二氧化硅包覆的金纳米团簇(silica-coated gold nanocluster,AuNC@SiO2),探讨以其为显像剂靶向胃癌MGC-803细胞荧光成像以及胃癌移植瘤模型中CT成像的双模式成像的可行性。 方法: 采用层层包硅法制备得到AuNC@SiO2,将其和肿瘤细胞标志物叶酸(folic acid,FA)偶联,MTT法检测偶联物AuNC@SiO2-FA对MCG-803细胞的毒性作用,激光共聚焦显微镜观察其靶向胃癌细胞荧光成像的可能性;以MG-803细胞皮下接种BALB/c裸鼠建立移植瘤模型,采用CT成像系统采集胃癌移植瘤内注射AuNC@SiO2前后的CT信号,探讨AuNC@SiO2在移植瘤模型中CT成像的可行性。 结果: 成功制备了形貌均一、分散性良好、具有良好荧光光学特性的AuNC@SiO2,AuNC@SiO2和AuNC@SiO2-FA在500 mg/ml时对胃癌MGC-803细胞和正常胃黏膜GES-1细胞的毒性均较低。在细胞学实验中,AuNC@SiO2-FA能够有效地靶向胃癌MGC-803细胞而非正常GES-1细胞,从而清晰地荧光成像;在裸鼠胃癌移植瘤模型中,肿瘤部位注射AuNC@SiO2后CT信号明显增强,HU值由注射前的129.16上升到383.32。 结论: AuNC@SiO2能够用于荧光和CT双模式成像,AuNC@SiO2-FA能靶向胃癌细胞荧光成像。
[Key word]
[Abstract]
Objective:To investigate the feasibility of targeted fluorescent imaging to MGC-803 gastric cancer cells and the potential of CT imaging of gastric cancer using nanocomposite probes of silica-coated gold nanocluster (AuNC@SiO2). Methods: The AuNC was coated by multilayer silica shells to obtain AuNC@SiO2. AuNC@SiO2 was conjugated with cancer cell targeted folic acid (FA), and AuNC@SiO2-FA was then used to investigate the feasibility of targeted fluorescent imaging to gastric cancer cells. MG-803 cells were injected subcutaneously into BABL/c nude mice to establish a cancer xenograft model. CT imaging was performed to collect CT signals before and after subcutaneously injection of AuNC@SiO2, thus exploring the feasibility of AuNC@SiO2 nanoparticles in CT imaging of tumor mouse models. Results: AuNC@SiO2 was successfully constructed with a uniform shape, good dispersbility and fluorescence optical properties. AuNC@SiO2 and AuNC@SiO2-FA showed a low cytotoxicity on gastric cancer MGC-803 cells and normal gastric mucosal GES-1 cells at a concentration of 500 mg/ml. The AuNC@SiO2-FA showed an effectively targeted ability to gastric cancer MGC-803 cells rather than normal GES-1 cells, thus presenting a clearly fluorescence imaging. CT signals were significantly enhanced in tumors after AuNC@SiO2 injection, with HU value increasing from 129.16 before injection to 383.32. Conclusion: AuNC@SiO2 can be used for fluorescence imaging and CT dual mode imaging. Moreover, AuNC@SiO2 conjugated with FA can realize gastric cancer cells targeted fluorescence imaging.
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[基金项目]
国家重点基础研究发展计划(973计划)项目资助(No. 2010CB933901);国家杰出青年基金项目资助项目(No. 881225010)