碳点-金属离子纳米组装体的构建及其在肿瘤诊疗中的应用研究

As a newly emerged fluorescence nanomaterials, carbon dots (CDs) have attracted considerable attention thanks to their numerous merits, such as unique optical properties, excellent biocompatibility, facile surface modification and potential photothermal/photoacoustic functions. Therefore, CDs exhibited greatly promising applications in photoactivated tumor theranostics. The small size character of CDs (usually <10 nm), however, prevents their effective accumulation in tumor sites. In this project, a strategy of fabrication of CDs-metal ions nano-assemblies is to be taken to solve the above-mentioned problem, and key factors that affecting the construction of nano-assemblies will also be studied in-depth. In order to fully play the functions of each assembly units, carbon dots with red/near infrared emission characteristics and metal ions (e.g., Fe2+/Fe3+,Cu2+) with chemodynamic therapy (CDT) function will be applied as the basic units to construct nano-assemblies. The assemblies could not only effectively enhance the EPR effects of CDs, but also utilize the inherent fluorescence/photoacoustic/photothermal and other characteristics of CDs and the CDT function of metal ions. More importantly, the assemblies could also be disassembled under the stimulation of tumor microenvironment, which facilitate the diffusion of functional components to deep tumor tissues and uptake by tumor cells, so as to improve the diagnosis and treatment efficiency. This study is expected to improve the values of CDs in the field of biomedical applications and provide new ideas for nanomedicine theranostics.

作为一类新型荧光纳米材料，碳点因其优异的光学性能、良好的生物相容性、易于表面修饰性及潜在的光热/光声等功能，在光激活肿瘤诊疗领域展现出巨大的应用潜力。然而，碳点的小尺寸特性（通常<10 nm）限制了其在肿瘤组织的有效富集。本项目拟通过构建“碳点-金属离子”组装体的策略解决上述问题，并深入研究影响组装体构建的关键因素。为了充分发挥各组装单元的功能，本项目拟采用具有红光/近红外发射特性的碳点与具有化学动力学治疗（CDT）功能的金属离子（Fe2+/Fe3+,Cu2+）作为基本单元构建纳米组装体。该组装体不仅可以有效提升碳点的EPR效应，同时能够充分利用碳点固有的荧光/光声/光热等特性及金属离子的CDT效应。此外，该组装体还可以在肿瘤微环境刺激下解组装，有助于功能组分向深层肿瘤组织的扩散及被肿瘤细胞摄取，从而提升诊疗效果。本研究有望提升碳点在生物医学领域的应用价值，为纳米医学诊疗提供新的思路。

碳点因其优异的光学性能、良好的生物相容性、可控的表面性能及光热、光敏等特性而在肿瘤诊疗领域展现出巨大的应用潜力。然而，碳点小尺寸的性质限制了其在肿瘤病灶部位的累积，进而影响其成像及治疗功能的发挥。本项目首先根据肿瘤诊疗的实际应用需求开发了兼具长波长荧光发射及光诱导治疗性能的碳点，建立了对碳点的表面性能、光学性能、潜在治疗性能等进行按需调控的有效方法；重点构建了两类碳点-金属离子组装体，充分发挥了碳点作为多功能主体的优势，对影响组装体系构建的关键因素进行了探究，明确了多种组装条件的影响，为该类材料的制备提供了可靠依据；拓展构建了碳点交联体、碳点-介孔硅及碳点-纳米凝胶复合体系，并针对肿瘤微环境进行了响应性设计，在提高材料治疗效果的同时降低了副作用；最终验证了上述碳点基复合材料良好的肿瘤累积效果及增强的治疗效应。本项目提出的以碳点-金属离子组装体为代表的碳点基复合材料构建策略，一方面解决了单独利用碳点肿瘤累积差的问题，另一方面发挥了复合单元的协同功能，提高了碳点基复合材料作为纳米诊疗制剂的应用价值。. 项目圆满完成了预定研究任务，在国际知名期刊发表论文8篇，申请中国发明专利2项，协助培养研究生4名。