面向肿瘤诊断的顺磁性无镉量子点的溶剂调控制备及性质研究

Paramagnetic non-cadmium quantum dots combining the unique optical property of quantum dots and T1 magnetic resonance contrast enhancement by paramagnetic ion doping, show great potential in multi-modality imaging of tumor in vivo. The optical and magnetic properties of paramagnetic non-cadmium quantum dots strongly depend on the nanocrystal size, composition and their distributions, however, it still remains challenging to achieve precise control over them. Against the ubiquitous large fluorescence spectrum width of multicomponent non-cadmium quantum dots with better biological safety, the current project proposes the solvent-regulated strategy, to manipulate the thermodynamics and reaction kinetics of quantum dots formation processes, in order to achieve the size and composition control, and further to narrow the fluorescence spectrum width. By taking paramagnetic Mn2+ doped I-III-VI non-cadmium quantum dots as the model material, the polarity and viscosity of solvent will be regulated, and their effects on the precursor reactivity and nanocrystal growth rate related thermodynamics and reaction dynamics will be explored respectively, in order to achieve uniform size and composition distribution of quantum dots, as well as their size and composition control. The influence of the size, composition and distributions of quantum dots on the optical and magnetic properties will be investigated, aiming at narrowing the fluorescence width and tailoring the above properties. Tumor specific dual-modal nanoprobes based on paramagnetic non-cadmium quantum dots will be constructed for highly sensitive and accurate optical/magnetic resonance imaging of tumor in vivo. This proposal aims to provide solid foundation for the application of paramagnetic quantum dots in early diagnosis of tumor.

兼具量子点独特光学特性和顺磁性金属离子T1磁共振弛豫性能的顺磁性无镉量子点，在活体肿瘤多模态成像方面展现出广阔的应用前景。顺磁性量子点的光学和磁学性质强烈依赖于晶体尺寸、组份及其分布，然而其精准调控仍然面临挑战。针对生物安全性较高的多元无镉量子点荧光半峰宽普遍较宽的问题，本项目提出溶剂调控策略，改变纳米晶体形成的化学热力学和反应动力学过程，以实现其尺寸和组份控制，进而窄化荧光半峰宽。拟以顺磁性Mn2+掺杂I-III-VI族无镉量子点为模型，通过调节反应溶剂极性和粘度，研究其对前驱体反应活性和晶体生长速率相关热力学和动力学的影响规律，以获得均匀尺寸/组份分布，同时实现量子点尺寸和组份可调；研究尺寸、组份及其分布对量子点光学及顺磁性的影响，窄化荧光半峰宽，优化平衡光学/磁学性能；构建肿瘤特异性双模态纳米探针，实现活体肿瘤的准确灵敏光学/磁共振成像，为顺磁性量子点在肿瘤早期诊断中的应用奠定基础。

顺磁性无镉量子点的光学和磁学性能调控是本项目的核心内容。兼具量子点独特光学特性和顺磁性金属离子T1磁共振弛豫性能、生物安全性优异的顺磁性无镉量子点，在活体肿瘤多模态成像方面有着巨大的应用前景。顺磁性量子点的光学和磁学性质强烈依赖于晶体尺寸、化学组成及其分布，然而其精准调控仍然面临挑战。本项目针对上述问题，深入研究了近红外发光可调、发光效率高、发光峰宽窄化的I-III-VI量子点的可控制备方法、相关机理和成像应用，取得了如下成果：1）发展了I-III-VI量子点近红外发光性能的有效调控方法，揭示了量子点的化学组成、配体效应、有机硫源对纳米颗粒形成热力学和生长动力学的影响机理及发光机制，实现了尺寸及化学组成可控，获得了高近红外发光性能的无镉量子点；2）通过壳层掺杂顺磁性Mn2+离子降低对量子点发光中心的影响，有效平衡了光学和磁学性能，获得了本征光学及磁学性能优异的顺磁性量子点；3）基于生物安全性优异的顺磁无镉量子点构建了肿瘤特异性的光学/磁共振双模态纳米探针，发展了活体肿瘤的高灵敏、高准确性的检测方法。本项目发展了本征光学/磁性双功能无镉量子点的制备方法，为肿瘤的早期精准诊断提供了新的策略。