基于共轭聚合物嵌入介孔二氧化硅光声探针的肿瘤成像与药物输运研究

Photoacoustic imaging is a fast 3D non-invasive imaging technique which is developing rapidly in biomedical applications recently. This technique provides a robust approach for the early diagnosis of tumor, study of the tumor growth and the monitoring of the tumor environment during the therapy. The design of novel near infrared (NIR) absorbing photoacoustic probes is one of the most important aspects in this field and obtained more and more interest in tumor theranostics. Aimed to avoid the low stability and potential toxicity of organic micromolecule and inorganic nanoparticles, this project will use narrow bandgap conjugated polymer as photoacoustic contrast agent to fabricate non-toxic tumor specific photoacoustic probes. The relationship between the structure of the conjugated polymer and their optical properties will be investigated in order to improve their photoacoustic imaging ability. With nanotechnology, the conjugated polymer will be encapsulated in mesoporous silica to achieve water solubility and the stability of molecular conformation in the complex environment. After the conjugation of tumor targeting molecules,the probe can recoginize the tumor cells and be used for photoacoustic tumor imaging. Meanwhile, with the high drug loading of mesoporous silica and photothermal ability of the conjugated polymer, the fabricated probe will be applied for photoacoustic imaging-guided cancer therapy. We hope this work will be beneficial for the development of photoacoustic imaging and nanotechnology in biomedical field.

光声成像技术是近年来在生物医学领域快速兴起的一种快速无损伤3D检测技术，为肿瘤的早期检测、研究肿瘤的生长过程和治疗监控等方面的提供了重要的手段。其中，新型近红外光声探针的开发是该领域的研究重点和难点之一，在肿瘤的诊疗中受到了越来越多的关注。针对常用光声造影剂如有机小分子及无机纳米材料光稳定性差、潜在毒性等缺陷，本项目拟开发窄带隙共轭聚合物作为一种新型无毒的光声造影剂用于构建肿瘤靶向的光声探针；研究聚合物结构与其光学性能的联系，提高其光声信号强度；利用纳米技术将共轭聚合物包封在聚乙二醇化的介孔二氧化硅中实现其水溶和分子构型在复杂环境中的稳定；通过具有特异性识别能力的生物分子的进一步偶联，实现光声探针对于肿瘤的靶向识别与成像；同时利用介孔二氧化硅的载药能力及共轭聚合物的光热能力，实现光声成像指导的靶向肿瘤治疗，为光声成像和纳米技术在生物医学领域的发展做出贡献。

以光声成像为代表的新型光学成像技术是近年来在生物医学领域快速兴起的一种高效检测技术，为许多疾病的诊断和疗效监控等提供了重要的手段。共轭聚合物因其良好的生物相容性、耐光漂白、光学性能可调、吸光系数高等优势，已被用于诸多光学成像探针的开发之中，受到了越来越多的关注。然而大部分共轭聚合物都是疏水的，因此本项目开发了一种普适的方法将共轭聚合物转入水相，同时又避免了传统两亲性聚合物包裹方法中空胶束的产生。本项目首先制备或筛选了多种在近红外光区有吸收或荧光性能的共轭聚合物，接着通过阳离子表面活性剂将这些疏水共轭聚合物转入水相，进行介孔二氧化硅的包裹以及聚乙二醇的修饰，从而获得复杂环境中性能稳定的光学探针，介孔二氧化硅也赋予了材料良好的载药性能；研究了相关材料的光学性能，并构建了多种光学诊疗平台，实现了活体肿瘤的光学成像及成像指导下的多模治疗。作为参照，本项目还制备了多种常见的无机纳米材料如硫化铜、硫化银等用于构建无机光学探针，同时比较了各种材料的优势和不足，为光学诊疗平台的进一步发展和应用提供了一定的指导。