NIR-II/MRI双模态聚合物分子刷的设计合成及肿瘤成像研究

近红外二区（NIR-II）/磁共振成像（MRI）双模态造影剂集高灵敏度、高时间分辨率的NIR-II荧光成像和高空间分辨率、无成像深度限制的MR成像功能于一体，克服了单一成像模式的不足，在肿瘤成像方面具有广阔的应用前景。但是现有的NIR-II/MRI双模态探针依然存在成像性能差和生物安全性低的问题。本项目拟以聚合物分子刷为载体，共价偶联NIR-II荧光分子、小分子钆基螯合物DTPA-Gd和靶向环肽RGD，构建生物安全性好的NIR-II/MRI双模态肿瘤靶向聚合物刷。并且通过调控主、侧链的长度以及NIR-II荧光分子、DTPA-Gd和RGD的比例，揭示双模态聚合物刷的结构与发光、弛豫性能的构效关系，为合理设计具有高荧光量子产率和高弛豫率的聚合物刷提供理论依据，提高成像灵敏度和准确度。本项目可为开发低毒、高性能的NIR-II/MRI双模态造影剂提供新思路，为肿瘤的精准诊断和手术导航提供技术支撑。

NIR-II/MRI dual-modal contrast agents integrate NIR-II fluorescence imaging with high sensitivity and time resolution and MR imaging with high spatial resolution and without imaging depth limit, which overcome the shortcomings of the single mode imaging and have a broad application prospect in tumor imaging. However, the existing NIR-II/MRI dual-modal probes still have poor imaging performance and low biosafety. In this project, NIR-II/MRI dual-modal tumor-targeted polymer brushes with good biosafety will be constructed by using the polymer brushes as the carrier and covalently conjugating NIR-II fluorescent molecules, small gadolinium-based compounds (DTPA-Gd) and cyclic peptides RGD. Meanwhile, the structural-activity relationship between the structure of the dual-modal polymer brushes and their luminescence and relaxation properties will be revealed by adjusting the lengths of main and side chains of the polymer brushes, and the composition ratio of NIR-II fluorescent molecules, DTPA-Gd and RGD, which could provide a theoretical basis for the rational design of polymer brushes with high fluorescence quantum yield and high relaxation rate, and improve the sensitivity and accuracy of imaging. This project will provide a new idea for the development of NIR-II/MRI dual-modal contrast agents with low toxicity and high performance, and provide technical support for accurate tumor diagnosis and image-guided tumor surgery.