具有光热治疗功能的CuS@聚合物核-壳结构纳米复合材料

Cancer poses a great threat to the human health, and the development of the technology for cancer therapy has attracted much interest. Near-infrared (NIR) laser-induced photothermal ablation therapy (PAT) is a novel and efficient therapeutic approach for cancers, but a prerequisite for the development of the practical application of PAT is to obtain efficient and biocompatible photothermal nanoagents. To address this problem, this project aims to develop CuS@polymer core-shell nanocomposites with excellent photothermal conversion property, biocompatibility and targeting ability. This project consists of four steps. The first step is to prepare CuS nanomaterials with excellent photothermal property, then to coat CuS nanomaterials with uniform and compact polymer shell by polymerization technologies, and to develop/optimize polymerization technology and growth mechanism of polymer shell. The second step is to conjugate targeted molecules on the surface of polymer shell for the preparation of nanocomposites with active-targeting, apoptosis targeting, and dual (active/apoptosis)-targeting. The third step is to measure and optimize the biocompatibility and target ability of CuS@polymer nanocomposites. The last step is to inject the tumor animals with nanocomposites solution, to determine the in-vivo distribution and metabolism of nanocomposites, and to investigate the volume change of the tumor and the ablation efficiency of cancer cells under the irradiation of NIR laser. This project will not only lay a foundation for the development of efficient and biocompatible photothermal nanoagents, but also make important contributions to the future clinical application of PAT technology and therefore the improvement of human health.

癌症严重威胁了人类的健康，如何治疗癌症吸引了广泛关注。近红外光激发的光热消融技术是一种新型高效的癌症治疗方法，但是其发展前提是开发响应近红外光的高效低毒光热转换材料。本项目旨在开发具有优异光热性能、生物兼容性和靶向性的CuS@聚合物核-壳结构纳米复合材料，并将其用于光热消融动物肿瘤。主要研究内容包括：(1)先制备CuS纳米光热材料，再利用聚合技术在CuS表面生长均匀致密聚合物壳层，发展和完善聚合物壳层的制备技术和生长机理；(2)在壳层表面连接靶向分子，构建主动靶向、凋亡靶向和双靶向纳米复合材料；(3)测试和优化纳米复合材料的生物兼容性和靶向能力；(4)将光热材料水溶液注入动物体内，分析光热材料在体内的分布和代谢过程，并在近红外光激发下探索肿瘤体积变化和癌细胞消融效果。本项目的成功实施将为发展高效低毒的光热转换材料奠定基础，也为光热治疗癌症技术将来走向临床应用和提高人民健康水平做出重要贡献。

近红外光驱动的光热治疗肿瘤技术已经吸引了高度关注，其发展关键是研发高效和生物相容性好的光热转换试剂。本课题旨在设计和制备用于肿瘤诊疗的CuS@聚合物核-壳结构以及其他类型半导体多功能光热转换材料。主要成果有：(1) 设计和制备了多种CuS@聚合物光热转换纳米材料，例如CuS@蛋白质、CuS-DOX@纳米凝胶、CuS@PDA-Gd-FA等纳米复合材料；将纳米材料水溶液注入老鼠肿瘤部位，近红外激光照射肿瘤10分钟左右，肿瘤区域的癌细胞即可被高效融化从而延长老鼠生命周期；(2) 设计和制备了多种其他类型的多功能纳米材料，例如钨基半导体（CsxWO3纳米棒、WS2纳米线等）、通过形貌调控（FeS2纳米颗粒）或掺杂（Nb-TiO2纳米晶、Sb0.2-SnO2纳米晶）构筑的多功能试剂等；实现了成像引导下的光热诊疗或者光热-化学协同治疗；(3) 制备了新型响应近红外光的光热转换薄膜，它们具有优异的可见光透过和近红外光屏蔽性能，可用作玻璃新型涂层；(4) 发展了其它类型光功能纳米材料，它们在生物、能源和环境等领域有较好的应用前景。以上成果对开发新型光功能材料和对恶性肿瘤的无/低副作用治疗具有重要意义，为将来减轻病人和社会医疗负担、提高人民健康水平和生活质量做出重要贡献。项目完成人共发表论文28篇，其中在Adv. Mater.、Adv. Funct. Mater.、Biomaterials等重要期刊上共发表SCI论文27篇。申请专利4项，另授权专利有5项。