H链铁蛋白介导的光磁双模式靶向探针的构建及肿瘤可视化成像研究

项目名称： H链铁蛋白介导的光磁双模式靶向探针的构建及肿瘤可视化成像研究

项目编号： No.81503038

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 姚寒春

作者单位： 郑州大学

项目金额： 17.9万元

中文摘要： 针对目前多功能纳米粒成像系统存在制备过程复杂、生物相容性差的问题，利用H链铁蛋白纳米笼既可作载体，又具有靶向性的特点，构建一种新型双模式成像探针。以H链铁蛋白纳米笼为载体，内部装载磁性四氧化三铁纳米粒，外部通过共价键偶联近红外发光碳点，无需修饰靶向试剂，实现光磁双模式成像。以混酸氧化及表面修饰的方法合成近红外荧光碳点；采用透射电镜、粒度分析仪、核磁共振光谱等技术对探针结构及性能进行表征；通过激光共聚焦显微镜观察其在MCF-7乳腺癌细胞中的摄取情况；MTT比色法检测探针对MCF-7细胞的毒性。以荷瘤裸鼠为模型，尾静脉注射成像探针，在不同时间点通过活体荧光成像和磁共振成像观察其对肿瘤组织的靶向成像效果及在小鼠体内的分布。该探针制备过程简单，生物相容性好，在H链铁蛋白介导下特异性靶向肿瘤细胞，实现双模式（近红外荧光/磁共振）成像及细胞追踪，为基于铁蛋白纳米笼的肿瘤成像与诊断提供新的思路和方法。

中文关键词： H链铁蛋白；碳点；近红外荧光；；靶向探针；双模式成像

英文摘要： Aiming at the problems that multifunctional nanoparticles imaging system have the complicated preparation process and poor biocompatibility, with the characteristics that H chain ferritin nanocages can be used as a carrier and targeted molecular, a new dual mode imaging probe was developed. Using H chain ferritin nanocages as a carrier, loading magnetic ferroferric oxide nanoparticles internally, and coupling of carbon dots with near-infrared emission externally by covalence, not modifying targeting agents, realize the optical and magnetic resonance dual mode imaging. The carbon dots with near-infrared fluorescence properties were synthesized based on the chemical oxidation in a mixture of concentrated acids and surface modification. Using TEM instrument, particle size analyzer, nuclear magnetic resonance spectroscopy to characterize the structure and properties of the probe; Observing the uptake of the probe in the MCF-7 breast cancer cells by confocal laser scanning microscope; Detecting the toxicity of probe to MCF-7 cells with MTT colorimetric assay. The nude mice bearing breast cancer were selected as a model. After injection of imaging probes in the tail vein, we observe the tumor targeting imaging effect and distribution in mice through the vivo fluorescence imaging and magnetic resonance imaging at different time. The imaging probe have the simple preparation process and good biocompatibility, through H chain ferritin specific targeting to the tumor cells, realize the dual mode (near-infrared fluorescence/magnetic resonance) imaging and cell tracking, and provide new ideas and methods for the tumor imaging and diagnosis based on the ferritin nanocages.

英文关键词： H chain ferritin ;Carbon dots;Near infrared fluorescence;Targeted probe ;Dual mode imaging