共轭高分子光声/CT肿瘤靶向成像探针及其光热疗的应用

Over recent years, photoacoustic probes with near infrared (NIR) absorption properties for targeted tumor imaging has been widely concerned. Although it can provide high contrast and deep tissue imaging, it suffers from the limited spatial resolution in anatomy, which restricted its clinical applications to some extent. Based on this, our project proposed to develop novel photoacoustic/CT dualmodality probes which combine high contrast and high spatial resolution together to improve the tumor detection performance. The functional groups-modified block conjugated polymers with native strong light absorption, photostability and biocompatibility are firstly prepared through controllable radical polymerization. Then the polyethylene glycol chains are introduced to endow good water-solubility and biocompatibility. Subsequently, the iodobenzene groups are linked to the flexible main chains to provide CT contrast properties. Then, the cancer-targeted function is studied on conjugated polymers modified with folic acid, which can target folate receptor, the highly expressed molecules on the tumor cell surface. Besides, the development of photothermal therapy against cancer using our probes is conducted by investigating the photo-thermal conversion performance based on their strong NIR absorption properties. Finally, the performance of the probes will be evaluated through investigating the folic acid-targeted dualmodality imaging and photothermal therapy in vivo. We hope this work will be beneficial to developing high-performance multimodal probes for applications in biomedical theranostics.

近年来具有近红外吸收性质的光声成像探针在肿瘤成像方面受到广泛关注。虽然其能提供高对比度和深组织成像，但在提供解剖学分辨率上仍有所欠缺，因此在一定程度上限制了临床应用。基于此，本课题提出开发一类新型近红外吸收共轭高分子光声和计算机断层扫描（CT）成像探针，通过引入CT成像技术在解剖学高空间分辨率来实现对肿瘤的有效检测。利用共轭高分子吸光性强、光稳定性好及生物毒性小的特性，通过可控自由基聚合制备富含官能团的嵌段聚合物，并进一步连接聚乙二醇来提高水溶性和生物相容性；随后在柔性主链引入碘苯基团赋予高分子CT造影性能；同时修饰对肿瘤细胞表面高度表达的叶酸受体具有特异性作用的生物分子叶酸，研究探针对肿瘤的靶向识别功能；利用高分子的近红外吸收特性，研究探针的光热转换性能，开发探针在肿瘤光热疗中的应用；针对裸鼠模型的肿瘤靶向成像和热疗，对高分子探针的效能进行评价，为高性能多模态探针在诊疗中的发展做出贡献。

多模态成像能够结合多种成像模式的优点并弥补各自的不足，从而提供更加准确丰富的影像学信息，在生物成像领域受到了广泛的关注。如光声成像能够实现高对比度和深组织成像，CT成像能够提供解剖学高空间分辨率，而近红外二区荧光成像具有高灵敏度高信噪比的优势。高分子材料因其优异的生物相容性和可修饰性为多模态探针的构建提供了一个高效的平台。本项目通过对高分子材料的主链设计、支链修饰、包埋改性等方面的研究，设计开发了多种可用于光声、近红外二区荧光或CT成像的多功能纳米诊疗体系，用于多模成像指导的肿瘤光热疗。我们将光声信号单元和CT 信号单元集合于同一高分子材料上，开发出既能提供高的空间和组织学分辨率又能提供高对比度的光声/CT双模成像探针；通过在共轭高分子中引入双受体，获得了在近红外二区具有良好光吸收的共轭高分子材料，实现了近红外二区光声成像指导的光热治疗；基于吡咯并吡咯二酮单元制备了多种在近红外一区具有强吸收，在近红外二区具有荧光发射性能的共轭高分子材料，并通过两亲性聚合物包裹或共嵌段的方式构建可用于近红外二区荧光成像/光声成像的多模态探针，用于肿瘤的高分辨成像和光热疗。本项目制备的多种多模态探针为纳米生物医学的发展提供了丰富的材料基础。