可生物降解聚集诱导发光高分子探针设计合成与生物应用

Aggregation-induced emission (AIE) is an abnormal fluorescence phenomenon. Basedon the AIE molecules, we can fabricate ultrabright fluorescent polymeric probes,which can effectively overcome the aggregation caused quenching (ACQ) effect of conventional organic luminogens. The preparation and biomedical applications of these AIE-active polymers have attracted great research attention recently..However, the information about biodegradable AIE-active polymeric probes has been seldom reported. Based on our research background, we proposed the fabrication of biodegradable AIE-active polymeric probes in this proposal for the first time. A series of biodegradable and multifunctional AIE-active polymeric probes were fabricated via the design of AIE-active molecules and fabrication strategies. The fluorescence properties, biodegradability as well as drug loading and controlled release behavior of these biodegradable AIE-active polymeric materials were inversitaged.The potential applications of these AIE-active polymeric probes for biological imaging, targeted drug delivery, cancer treatment and nanotheranostics were also explored. In conclusion, this proposal provided some new ideas for the fabrication of biodegradable AIE-active polymeric materials, which are expected to overcome the drawbacks of long term bioaccumulation and toxicity of normal AIE-active polymeric materials. On the other hand, this proposal will further promote and expand the biomedical applications of AIE-active polymeric materials.

聚集诱导发光（AIE）是一种反常的荧光发射现象。利用AIE分子的荧光增强性能，可以构建出高荧光强度的高分子荧光材料，从而克服常规有机荧光分子的聚集荧光淬灭效应。近年来基于AIE分子的高分子荧光探针研究引起了人们的极大兴趣，但是基于AIE分子的可生物降解高分子材料的构建和应用鲜见报道。本项目以申请人以往的研究工作为基础，提出了构建可生物降解AIE高分子纳米诊疗体系的研究思路。通过AIE分子的设计和高分子材料构建策略的选择，制备一系列可生物降解的多功能AIE高分子材料。考察这些材料的荧光性质、生物降解性能、药物载带和释放行为，探索其在生物成像、药物靶向输运、控制性释放、疾病治疗以及纳米诊疗等方面的应用。本项目首次提出了构建可生物降解AIE高分子材料的研究思路，有望克服常规AIE高分子材料在体内的长期蓄积和毒性问题，将有利于进一步拓展AIE高分子材料生物医学应用研究。

本项目针对聚集诱导发光高分子纳米材料应用的安全性问题，提出了多种构建可生物降解聚集诱导发光高分子纳米材料的方法。研究了这些材料在荧光成像、多模成像以及光动力治疗和药物输运方面的应用。系统发展了基于细胞微环境的生物降解、基于外界光源的光控荧光高分子纳米材料降解策略，相关成果在Advanced Science, Research, Chemical Engineering Journal，Carbohydrate Polymers等期刊发表论文多篇。以上研究结果对于拓展聚集诱导发光荧光纳米材料的体内生物应用有重要的参考意义，也将推动相关领域的发展。