骨靶向性近红外荧光诊断试剂的设计、合成与活性评价

项目名称： 骨靶向性近红外荧光诊断试剂的设计、合成与活性评价

项目编号： No.81502932

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： 包凯

作者单位： 沈阳药科大学

项目金额： 18.5万元

中文摘要： 随着我国人口老龄化的发展，骨关节疾病成为当前常见疾病之一，严重威胁着人们的健康。近红外荧光成像是一种新颖的光学成像技术，其中骨靶向性近红外荧光诊断试剂已成为骨组织光学成像研究的热点和前沿。尽管骨靶向性近红外荧光诊断试剂的研究近年来取得了巨大进展，但仍存在靶向性不够突出、体内活性不够理想以及构效关系尚未明确等重要的科学问题亟待解决。在前期工作的基础上，我们提出了多共价结合骨靶向性的诊断试剂设计策略，拟将骨靶向性双磷酸类化合物中的磷酸基团片段或者单个磷酸基团引入到五甲炔花菁和七甲花菁荧光试剂的分子骨架上，重点设计、考察磷酸基团的片段的种类、数量、位置以及荧光试剂分子骨架上取代基变化对诊断试剂的理化、光学性质和靶向性的影响。在完成构效关系分析的基础上，发现结构新颖、骨靶向性突出的近红外荧光诊断试剂，为创制拥有自主知识产权的骨靶向性诊断试剂奠定基础。

中文关键词： 诊断试剂；骨靶向；近红外荧光试剂；构效关系

英文摘要： With the development of chinese aging population, joint diseases become one of the common diseases and a serious threat to people's health. Near-infrared fluorescence imaging is a new optical imaging technique and bone targeted near-infrared contrast agent has been a research frontier and hotspot of bone imaging. Although great progress has been made in recent years, there are still challenges in this field including not ideal targeting capacity and in vivo activity, and unclear structure-activity relationship. On the basis of our previous work, we propose a new design strategy named Multivalent Bone Targeting. It bases on the incorporation of targeting moieties of BPs or a single phosphoric acid fragment of BPs into the non-delocalized structure of pentamethine and heptamethine indocyanines. Focus will be concentrated on the influence of targeting phosphate groups' type, number, location and substituent changes of the fluorophore's skeleton on the physical, chemical, optical properties and bone targeting efficiency of the contrast agents. The completion of this project will led to a better understanding of the structure-activity relationship, provide novel contrast agents with increased binding capacity, and lay the foundation for the development of next generation of bone targeted near-infrared contrast agents.

英文关键词： Contrast Agents;Bone Targeting ;Near-Infrared Fluorophore;structure-activity relationship