基于柱芳烃构筑的双重刺激响应多功能纳米药物载体用于癌症光声成像及靶向治疗研究

The early diagnosis and treatment of cancer is a great challenge for cancer therapy. Recently, the rapid development of nanotechnology provides an effective way for the treatment of cancer. In particular, developing multifunctional nanoparticles which could integrate targeting, imaging diagnostic and therapy together has become a research highlight in the field of cancer therapy. Photoacoustic imaging technique without radiation and damage has been developing rapidly in recent years and quickly introduced into cancer imaging. In this project, photoacoustic imaging is innovatively introduced to develop smart nanocarriers for the treatment of cancer. A novel water-soluble pillar[5]arene-based amphiphile will be synthesized, which could self-assemble into dual pH- and hypoxia-responsive vesicles in water to encapsulate drug molecules. More significantly, benefiting from the specific host-guest interaction of pillar[5]arene, the obtained vesicles can be successfully functionalized with targeting ligands and photoacoustic imaging probes in a facile, nondestructive, and modular manner.The results of photoacoustic imaging can be used to evaluate the targeting ability of the nanocarriers and guided for cancer therapy. The implementation of the project is expected to develop novel multifunctional drug delivery nanoplatform for photoacoustic imaging and therapeutics which will promote the development of diagnostics and treatment of cancer, and provide new ideas for the realization of personalized detection and treatment.

目前癌症的早期诊断与治疗已经成为临床急待解决的关键问题。纳米技术的发展为癌症的治疗提供了有效途径，开发集靶向、医学成像和治疗于一体的多功能纳米药物载体用于癌症早期诊疗已经成为目前研究的热点和难点。光声成像技术是近年来快速发展的一种非辐射、无损伤生物医学成像手段，被迅速用于癌症成像研究中。本项目创新性地将光声成像技术引入，开发具有靶向、光声成像诊断及治疗一体化的智能纳米药物载体，拟合成具有pH及乏氧还原酶双刺激响应性的基于水溶性柱[5]芳烃的两亲性单体，两亲体在水中自组装成囊泡且可以对抗癌药物进行负载和可控释放；利用柱[5]芳烃的主客体作用力可以方便的修饰上靶向配体及光声成像探针，通过光声成像评价癌症的靶向治疗效果，为优化癌症治疗方案提供支撑。课题的实施有望开发光声成像引导下具有癌症靶向治疗的智能纳米药物载体，推动癌症早期诊疗事业的发展，为实现个性化治疗提供新的思路。

目前癌症的早期诊断与治疗已经成为临床急待解决的关键问题。纳米技术的发展为癌症的治疗提供了有效途径，开发集靶向、医学成像和治疗于一体的多功能纳米药物载体用于癌症早期诊疗已经成为目前研究的热点和难点。本项目设计合成近红外吸收的芘酰亚胺客体，利用水溶性柱[5]芳烃与该客体的主客体作用力构筑一例pH响应的超分子囊泡用于癌症的光热/化疗联合治疗；进一步利用水溶性柱[5]芳烃的主客体作用力构筑一例新型多功能超分子囊泡，实现了癌症光热/光动力/乏氧激活化疗的联合治疗。光声成像技术是近年来快速发展的一种非辐射、无损伤生物医学成像手段，被迅速用于癌症成像研究中。作为另一种新型光学成像技术，近红外二区（NIR-II，1000~1700 nm）荧光成像具有更深的组织穿透深度和更高的空间分辨率等优点而受到人们广泛的关注。尽管目前光学诊疗技术得到了较大的提高，然而仅通过单一模态的光学成像或单一模态的光学治疗仍然很难达到高效地肿瘤诊疗效果。另外目前的光学诊疗平台存在组分复杂、需要多种波长激光等缺陷，因此急需设计开发单一波长激光触发的新型光学诊疗体系用于肿瘤的高效诊疗。基于此，申请人设计开发了系列有机小分子半导体材料，成功实现了单一波长激光触发的癌症靶向诊疗，该多功能光学诊疗平台的设计、开发为癌症早期诊疗领域研究提供了有效的理论依据。