多色碳点的可控合成及其在肿瘤标志物联合检测中的应用

Multicolor fluorescence labeling technology has attracted much attention to achieve fast, high efficient and accurate early diagnosis of tumor, which have put carbon dots (CDs) in the spotlight. Currently, most of the CDs are either blue or green and lack the ability of emitting long wave length florescence. The functional modification of CDs is difficult and their application in multicolor fluorescent labeling and biological imaging is limited. Since heteroatom doping may improve the intrinsic property of CDs, the multicolor CDs will be synthesized using proper carbon sources and doped with lanthanide metal or semi metallic elements. We will characterize the morphology, size and functional groups of the doped CDs. The effect of doping atoms on the luminescent properties of CDs and the nature of the luminescence will be studied. The CDs synthesized with defined doping atoms will be used for biological imaging and the detection of multiple tumor markers. This project aims to synthesize multicolor CDs doped with heteroatoms and having excellent optical properties. The mechanisms that the doping atoms affect the fluorescence properties of CDs will investigated. The results will make a great contribution to the knowledge of fluorescent nanocluster synthesis and Fluorescent labeling chemistry.

为了快速、高效、准确地进行肿瘤早期诊断，人们致力于研发多色荧光标记技术和肿瘤靶向荧光探针。近年来碳量子点成为人们关注的新发光材料。但由于目前所制备的碳点大多是蓝色或绿色，缺少长波长发射；且碳点修饰也是一个难点，这些都限制了碳点作为荧光标记物用于生物医学分析中。本项目基于元素掺杂可改变碳点性质，拟通过选择合适的碳源，以镧系金属元素或半金属元素掺杂制备多色碳点。在表征形态、粒径、表面官能团并比较不同掺杂碳点发光性质的基础上，归纳出异原子对碳点光学性质影响的规律、揭示其发光本质，达到可控合成多色碳点的目的；最后将多色碳点用于荧光标记的肿瘤标志物联合检测中，并将碳点用于肿瘤细胞靶向识别和成像。项目以合成光学性质良好的异原子掺杂多色碳点荧光探针为目标、以解决异原子对碳点荧光性质影响机理为关键科学问题，以碳点修饰为关键技术，不仅对荧光团簇纳米材料合成有指导作用，同时对荧光标记化学有十分重要的意义。

碳点作为良好的荧光探针仍然存在一些缺陷：发射峰位于红色和近红外区的碳点相对较少，不容易进行表面基团修饰使得其应用受到一些限制。本项目旨在弄清楚碳点的发光机制后，选择多种碳源实现可控合成包括红色在内的各种颜色碳点；并最终将其用于肿瘤标志物的检测。.按照预期计划，项目主要取得以下进展：.1）通过选择各种碳源，如柠檬酸、柠檬酸钠、柠檬酸铵、氨基吡嗪、硫脲、碳酸氢铵、硫氰酸铵、半胱胺盐酸盐、组氨酸合成多种碳点，并对其发光机理进行了一定程度的分析阐述。.2）利用碳点为荧光探针检测多种药物和生化物质，或将其用于细胞成像等，检测对象包括鸟嘌呤、N-乙酰半胱氨酸、抗坏血酸、利福平、姜黄素、绿原酸、黄芩苷、木犀草素、咖啡因、鞣酸、日落黄等等。.3）为了实现碳点作为荧光探针进行肿瘤的早期诊断，将碳点进行DNA修饰后，灵敏的检测前列腺癌肿瘤标志物前列腺特异抗原PSA。而且搭建的平台通过更换修饰碳点所用的待测物适配体即可以用于癌胚抗原CEA和小分子ATP的检测。另外，结合量子点和碳点双信号实现了肿瘤标志物MiRNA-141和MiRNA-21的联合检测。