基于共轭高分子的pHe敏感型NIR-II肿瘤光学成像探针及光热疗的研究

新型近红外II区（NIR-II, 1.0-1.7 um）荧光成像技术相较于传统近红外（650–950 nm）成像技术具有更高光学对比度、更深组织穿透深度等优势而在肿瘤诊疗方面迅速受到关注。但该类技术目前缺乏穿透深度深、生物相容和光稳定性好、肿瘤智能靶向的NIR-II成像探针。因此，本课题提出开发基于共轭高分子的pHe敏感型NIR-II成像探针，即利用共轭高分子光稳定性好、吸光性强等特性，开发800 nm吸收（穿透深度深）的共轭高分子链，通过可控自由基聚合引入肿瘤微环境pHe响应基团，继而连接聚乙二醇提高其水溶性和生物相容性；研究肿瘤pHe刺激下该探针聚集态及相关NIR-II信号的变化以及由此产生的对广谱肿瘤的识别能力；并利用探针近红外光吸收的能力用于光热疗；使用裸鼠模型评价探针肿瘤靶向成像和治疗能力，发展NIR-II成像指导光热疗于一体的肿瘤诊疗模式，推动相关光学技术在生物医学领域应用。

Compared to the conventional near-infrared (NIR, 750–900 nm) imaging, New NIR-II (1.0–1.7 mm) fluorescence image has attracted much interest recently owing to higher spatial resolution at deeper tissue penetration depths. However, shortcomings of existing NIR-II fluorophores include relatively weak 800 nm absorption，low optical stability and biocompatibility，Smart response of tumor microenvironment .According to the above requirements, our project proposed to develop novel NIR-II fluorescence image probes based on water soluble conjugated polymer with a rapid response intelligent diagnostic system for tumor microenvironment. Firstly, the tumor targeting based on pHe responsive functional groups-modified block conjugated polymers with native strong 800nm absorption and photostability are firstly prepared through controllable radical polymerization. Then the polyethylene glycol chains are introduced to endow good water-solubility and biocompatibility. Secondly, the NIR-II fluorescence signal and aggregation relationships are investigated under different tumor microenvironment. In the meantime, we capitalized on the acidic, tumour microenvironment pHe to achieve the detection of tumour tissues in a broad range of mouse cancer regardless of their genotypes and phenotypes. 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 NIR-II fluorescence imaging and photothermal therapy in vivo. We hope this work will be beneficial to developing high-performance NIR-II fluorescence probes for applications in biomedical theranostics.