精氨酸的能量转移型复合纳米近红外比率荧光探针及其生物成像

As a kind of conditional essential amino acid, arginine is widely involved in cell metabolism, cell cycle regulation, immune regulation, hormone secretion, protein metabolism, wound healing, intestinal mucosal barrier maintenance, and so on. Low concentration of arginine promotes the growth of liver cancer cells, and high concentration of arginine inhibits the growth and proliferation of hepatocellular carcinoma cells. Therefore, it is of great significance to detect the concentration of arginine at the level of cell, tissue and organ for further studying the function of arginine in biological tissues..In this project, through clear design and synthesis of molecules, and clarifying the inner relationship between structure and properties, several asymmetric dimethine cyanine derived NIR fluorescent molecular probes will be obtained toward arginine. By adjusting the type and concentration of the doping element and chemically modifying the surface, the emission spectra and the biocompatibility of rare earth nanoparticles will be controled and optimized relatively. With assemblying and covalent bonding, a series of organic-inorgance hybrid nanomateries will be fabricated. The study of organic molecular structure and nano particles surface modification method on both energy transfer efficiency and recognition performance will be focused on, The interactional chemical mechanism of the composite fluorescent nanoprobes and arginine in the intra cell or tissues will be clarified, and NIR ratio fluorescent recognition and imaging of arginine in cells, tissues and organs will be realized. This work is of great significance for the development of new fluorescent probes.

精氨酸广泛参与细胞代谢，机体的循环调节、免疫调控、激素分泌、蛋白代谢、创面愈合及肠道粘膜屏障维护等过程。低浓度精氨酸可促进肝癌细胞的生长，而高浓度的精氨酸抑制肝癌细胞的生长和增殖。因此，在细胞、组织和器官层面上对精氨酸在生物体内实时的浓度检测和成像对进一步研究其在生物组织内的功能具有重要的意义。.本课题拟通过明确的分子设计与合成、揭示结构与性质的关系，得到对精氨酸具有高灵敏和高选择性的不对称二甲川菁类有机分子荧光探针。此外，申请者拟通过调节掺杂元素的种类和浓度来调控稀土上转换纳米粒子的发射光谱，并对其表面进行化学修饰，使其和有机分子探针进行复合。重点研究有机分子结构和纳米颗粒表面修饰方式对能量转移效率和识别性能的影响，阐明复合纳米探针与精氨酸在细胞或生物组织内部相互作用的化学机制，实现对细胞、组织和器官内精氨酸的近红外比率荧光识别和成像。该工作对发展新型荧光探针具有重要意义。

按照原计划要求，结合本领域内最新研究发展，本项目通过优化实验条件，合成了具有定位功能的、基于半菁的对精氨酸有选择性识别的反应型有机分子荧光探针，研究了溶液中pH、金属离子、阴离子、生物小分子等对分子探针识别精氨酸的影响，并研究了识别机制；在此工作基础上，我们又考察了分子荧光探针在细胞中的毒性、定位效果和对精氨酸的识别效果；基于有机分子探针识别精氨酸前后紫外-可见吸收光谱的变化，制备了具有良好形貌和较高发光量子产率的稀土上转换纳米颗粒；在以上工作基础上，将有机分子荧光探针与稀土上转换纳米粒子进行组装，得到了具有能量转移的有机-无机复合纳米材料，系统研究了溶液中复合材料的光稳定性、热稳定性和微环境对其识别效果的影响，并研究了细胞中复合材料的毒性、定位效果和发光识别效果。得到了近红外光激发、荧光共振能量转移型肼的高灵敏性、高选择性比率复合纳米荧光探针。