近红外CuInSe2量子点的制备及其在肿瘤成像上的应用研究

To date, in vivo tumor fluorescence imaging, including low signal-to-noise caused by the background fluorescence, poor targeting capability caused by the lacking of specific ligands, insensitive deep tissue imaging caused by the fluorophore emission wavelength in the visible area. Based on the previous researches, we will synthesize the high quantum yield CuInSe2 near-infrared quantum dots (NIR QDs) in this project, which supported by sol preparation low-toxic CuInSe2 nanocrystals technology and by means of the defects of CuInSe2 regulation, following with doping and surface functionalization of the as-prepared CuInSe2 QDs to achieve high stability and good biocompatibility. Fabrication of near-infrared fluorescent quantum dots-based biological activity probes through biological coupling technique and tumor targeting ligands coupling, which applied to the tumor cells and the targets in vivo imaging, and to promote the development of fluorescence imaging in the diagnosis, treatment and monitoring of tumor.

针对目前肿瘤在体荧光成像诊断技术存在背景荧光信号而造成的灵敏度低，所用探针缺乏特异性而造成的靶向性差，荧光探针中的荧团发射波长处于可见光区而造成的深部组织显像不灵敏等缺陷。本课题拟在前期工作基础上，以溶胶制备低毒CuInSe2纳米晶技术为支撑，以CuInSe2的缺陷调控为手段，通过适当的掺杂及对表面进行功能化修饰改性，制备得到高稳定性、高生物相容性、高量子产率的CuInSe2近红外量子点。通过生物偶联技术与肿瘤靶向性配体偶联构建具有生物靶标活性的近红外量子点荧光探针，应用于肿瘤细胞成像和活体靶标成像方面，从而推动荧光成像技术在肿瘤诊断、治疗和监测中的发展。

目前肿瘤已成为人类主要的死亡原因，攻克肿瘤的关键在于提高早期诊断的准确率。肿瘤在体荧光成像诊断技术存在由活体在外源激发光下产生的背景荧光信号而生成的灵敏度低，所用探针缺乏特异性而造成的靶向性差。基于此，本项目以溶胶制备低毒CuInSe2量子点技术为支撑，结合I-III-VI族量子点的结构特征，以缺陷调控为手段，引入外源元素掺杂调控本征缺陷或构建核壳结构合成一系列近红外量子点，如Zn-CuInSe/S、Mn-ZCISe、ZnS@CuInSe2、ZnS@Zn-CuInSe等。通过修饰、包覆手段，结合表面基团替换、生物偶联技术对疏水性掺杂CuInSe2量子点表面进行改性研究，不但能够调控表面缺陷，还能调控量子点亲水性。最后辅以特异性的生物靶标分子修饰（选取胆管癌组织中BDNF为靶标分子），构建具有生物靶标活性的近红外荧光探针（Anti-BDNF-QDs），应用于肿瘤细胞成像（人胆管癌细胞系、QBC939），从而推动荧光成像技术在肿瘤诊断、治疗和监测中的发展。