用于癌症诊疗一体化的聚集诱导发光材料的构建及其性能研究

Among numerous advances that have been made, cancer theranostics that allow the ingenious integration of accurate diagnosis with targeted therapeutics in a single formulation within spatial colocalization, have aroused increasing attention in both research and clinical fields. Comparing with conventional theranostic materials, compounds having aggregation-induced emission (AIE) characteristics have been demonstrated to possess intrinsic advantages in terms of fluorescence imaging, photoacoustic imaging, photodynamic therapy, and photothermal therapy. However, the development of facile routes to AIE-active materials with extraordinary theranostic properties remains an urgently needed and challenging task facing scientists.. This project will mainly focus on the synthesis of a series of near-infrared AIE luminogens (AIEgens) through a simple protocol involving a few step reactions. Some analytical methods including NMR, HRMS, UV absorption, PL, photoacoustic analysis, DFT calculation and molecular behavior simulation, will be further utilized to investigate their molecular structures, AIE properties, ROS generation, photoacoustic property, as well as photothermal property. In addition, other studies on cancer-cells- and/or tumor-targeting, fluorescence imaging, photoacoustic imaging, photodynamic therapy and photothermal therapy, will be performed. Furthermore, some of the AIE materials will be employed for cancer theranostics involving multimodal imaging and therapy.. This project will stimulate novel theranostic agents for potential clinical applications, and provide useful insights into the design of well-performed theranostic materials with AIE features.

诊疗一体化是目前癌症防治领域最为活跃的研究方向之一。与传统的用于诊疗一体化的材料相比，聚集诱导发光材料在荧光成像、光声成像、光动力治疗和光热治疗等方面都具有显著优势，但是开发能够简单合成的、用于癌症诊疗实际应用的聚集诱导发光分子是一个极大的挑战。. 本项目拟开发简单的合成方法，来制备一系列近红外发光的聚集诱导发光分子，考察其分子结构、聚集诱导发光特性、产生活性氧能力、光声性质和光热性质。研究这些分子对癌细胞或肿瘤的靶向特异性、荧光成像及光声成像效果，并考察这些材料在体外活细胞和小鼠活体层面的光动力和光热治疗效果。并且，研究聚集诱导发光材料在多模态成像诱导多模态治疗方面的应用。. 本项目的执行将会促进新型诊疗一体化有机分子的发展，为研究具有优异的癌症诊疗性能的聚集诱导发光材料的设计、结构与性能提供实验基础。

诊疗一体化是目前癌症防治领域最为活跃的研究方向之一。与传统的诊疗一体化材料相比，聚集诱导发光材料在荧光成像、光声成像、光动力治疗和光热治疗等方面都具有显著优势，但是开发能够简单合成的、用于癌症诊疗实际应用的聚集诱导发光材料依然是一个极大的挑战。本项目开发了多种简单的合成策略，制备了一系列近红外发光的聚集诱导发光材料，证实了它们相比于传统诊疗材料的优越性；阐明了分子结构与细胞器靶向功能、光敏性能、光热转化性能之间的构效关系；实现了对动物活体的肿瘤靶向成像，以及对肿瘤多模态光学诊疗；提出了“Aggregation-Enhanced Theranostics”（聚集增强诊疗）的概念。通过本项目的实施，共发表论文36篇，其中影响因子大于10的论文27篇，包括Angew. Chem. Int. Ed. 6篇、J. Am. Chem. Soc. 1篇、Adv. Mater. 6篇、Matter 1篇、Adv. Funct. Mater. 4篇、Acc. Chem. Res. 1篇、Chem. Soc. Rev. 1篇、Biomaterials 4篇、Chem. Sci. 1篇等，以上论文中有“ESI高被引论文”7篇。申请相关专利4项。此外，通过本项目的实施，培养了研究生2人，本科生5人；参加国际国内学术会议8人次。

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