光控AIE共轭聚合物纳米药物的构建与抗肿瘤应用

The precise control of materials optical properties and the development of intelligent nanomedicine based on chemical strategy is the key issues for the precision medical treatment. In view of the previous studies, we propose to construct the light-controlled nanomedicine based on aggregation induced emission (AIE) conjugated polymer, to develop the combined treatment of potodynamic therapy (PDT) and chemical therapy with high efficiency. The donor-acceptor conjugated skeleton based on AIEgens endows the polymers with high quantum yield efficiency, effect reactive oxygen species (ROS) generation, and strong light-induced radical generation, which would possess well antitumor ability under both normal and hypoxia microenviroments. What’ more important, the introduction of ROS-responsive prodrugs on the surface of nanoparticles made by AIE conjugated polymer would realize the drug release upon light irradiation, meanwhile, enhanced permeability and retention effect could passively target the tumor in vivo. As a result, the high efficiency of antitumor would be realized based on the combined treatment of PDT and chemical therapy. This project aims at the well design of the optical properties of AIE conjugated polymer with the utilization of light-controlled drug release, and the development of intelligent nanomedicine could provide the new materials and strategy for effective antitumor applications.

利用化学手段精确调控材料光学性能并发展智能纳米药物是新一代精准医疗中的关键科学问题。基于前期工作，本项目拟提出基于新型聚集诱导发光（AIE）共轭聚合物的光控智能纳米药物的新思路，旨在发展高效光动力治疗联合可控化疗的新型高效抗肿瘤材料。通过设计并制备基于AIE基元的D/A型共轭聚合物，赋予该体系在聚集态下同时具有高的发光效率、高的活性氧（ROS）产生效率及强的光致自由基产生性能，使该材料体系可在正常条件和乏氧环境下均能有效杀伤肿瘤细胞。更为重要的是，在该AIE共轭聚合物材料组装所得的纳米材料表面偶联ROS响应性抗肿瘤前药，以此实现EPR效应被动靶向肿瘤后光控药物激活，有效联合光学治疗和化疗，实现高效抗肿瘤目的。该研究致力于新型AIE共轭聚合物材料的光学活性设计，通过进一步联合光激活手段，发展复合型智能纳米体系，为实现可控、智能和高效的肿瘤治疗提供新的材料体系和新模式。

高分子发光材料作为一类重要的功能材料，已在能源、健康和国防等高科技领域发挥了重要作用，如何基于分子构效关系系统性研究并提高高分子材料在聚集态时的发光性能，并实现特定的生物学功能和疾病的靶向治疗是目前亟待解决的挑战性问题。本项目以高分子化学为基础，将功能高分子材料与聚集诱导发光（Aggregation-Induced Emission，AIE）效应有机结合，构建功能AIE高分子材料。其既具备了功能高分子材料的优势，又兼顾了AIE材料的光学特征，能够有效利用生理环境中分子聚集过程构筑高性能光学材料。基于共轭聚合物的构建及应用研究为基础，通过分子工程技术，构建了系列新型AIE功能单体，基于分子构效关系的系统研究，通过多途径构建了靶向性功能AIE聚合物体系；依靠对内质网等亚细胞的选择性识别及微生物、活细胞等靶向成像及相关生理过程的动态示踪，揭示了相关生理过程，并进一步实现了对微生物及肿瘤的高效抑制，为构建高性能光功能高分子材料并实现靶向诊疗应用提供了有效的理论依据。