基于靶向TCP-1多肽的多功能超顺磁氧化铁纳米粒子用于结肠癌早期诊断和治疗的研究

项目名称： 基于靶向TCP-1多肽的多功能超顺磁氧化铁纳米粒子用于结肠癌早期诊断和治疗的研究

项目编号： No.81201085

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 影像医学与生物医学工程

项目作者： 王建浩

作者单位： 常州大学

项目金额： 23万元

中文摘要： 核磁共振成像是目前结肠癌诊断最有效的方法，其中最关键的步骤是造影剂的制备，然而现阶段缺乏针对结肠癌的特异性造影剂。TCP-1多肽是我们通过体内噬菌体展示技术和原位结肠癌动物模型相结合筛选出的一种新型结肠癌肿瘤靶向多肽。本课题在前期研究的基础上，以靶向TCP-1为中心研究对象，旨在研制一种针对结肠癌的早期诊断和治疗的新型造影剂，TCP-1将引导粒子特异性地结合并进入肿瘤的新生血管壁细胞，使用非侵入性的磁共振显影联合远红外荧光成像将可以实现小至几个毫米的早期肿瘤检测；同时，我们也计划将抗癌药物阿霉素通过腙键连接到TCP-1修饰的纳米颗粒的表面，经细胞内吞后，内吞体中的低酸性导致阿霉素的释放将引起肿瘤血管壁细胞的凋亡，从而杀死肿瘤。研究结果不仅可以有效促进结肠癌磁共振基础研究的发展，并且对疾病的诊断和治疗方案制定具有极为重要的意义，临床应用前景广阔。

中文关键词： 超顺磁氧化铁纳米粒子；靶向多肽；磁共振显影；结肠癌；早期诊断

英文摘要： The lack of specific contrast agents for colorectal cancer currently limits the use of MRI in diagnosis of colorectal cancer, which is heavily relied upon as the most effective imaging method. Developing a non-toxic and specific contrast agent towards colorectal cancer is thus in urgent need. Our team previously discovered a noval specific tumor homing peptide, called TCP-1 using in vivo phage display and orthotopic colorectal cancer animal model. Based on this discovery, we herein propose to develop TCP-1 targeted multifunctional SPIO nanoparticle SPIO-TCP-1-Cy5.5, to achieve colon cancer-specific active targeting, for the specific detection of colorectal cancer by MRI/infrared imaging and active SPIO mediated drug delivery. When intravenously injected to mice carrying orthotopic colorectal tumors, SPIO-TCP-1-Cy5.5 will specifically accumulate on and enter inside the cancerous new blood vessel cells. Tumors even with sizes as small as a few millimeters at early developing stages could thus be detected by non-invasive MRI and infrared fluorescence imaging. We also plan to conjugate doxorubicin to TCP-1 modified nanoparticles through an acid sensitive hydrazone bond. TCP-1 will guide the particles into new blood cells around colorectal tumors. After endocytosis, the low acidity in late endosome (pH ~ 5.5) will le

英文关键词： Superparamagnetic iron oxide nanoparticles；Targeting peptide；Magnetic resonance imaging；Colorectal cancer；Early diagnosis