聚多巴胺仿生交联AIE纳米诊疗体系构筑与应用研究

利用简单高效的方法，构建集成像和治疗为一体的多功能性纳米诊疗体系已成为当今纳米生物医学研究的重要方向和前沿领域。以贻贝仿生化学和聚集诱导发光(AIE)纳米探针构建领域的工作为基础，我们首次提出了利用贻贝仿生化学构筑聚多巴胺(PDA)交联的AIE荧光纳米诊疗体系的研究思路。通过AIE染料的设计，制备多种含有AIE染料和多巴胺的高分子；利用多巴胺的氧化自聚性质，实现AIE纳米颗粒的仿生交联。结合PDA的光热效应，探索PDA交联型AIE纳米诊疗体系在肿瘤热疗中的应用。另外，利用PDA的高化学反应活性，我们还可以将功能性高分子、治疗性成分、靶向基团通过Michael加成反应连接到AIE纳米颗粒表面上。再从细胞和动物层次研究其生物成像、药物载带和控制性释放及靶向性能；进而考察其代谢动力学行为、生物安全性和抗肿瘤效果。本项目不仅有利于深入理解贻贝仿生化学，也将为多功能纳米诊疗体系的构筑提供新的思路。

Facile preparation of multifunctional nanotheranostic systems is one of the frontier and hot research field in nanomedicine.Based on our research background in mussel inspired chemistry and aggregation induced emission (AIE) bioprobes, we proposed the ideas for fabrication of multifunctional polydopamine (PDA) cross linked AIE nanotheranostic systems via mussel inspired chemistry for the first time. Take advantage of the self polymerization of dopamine under alkaline solution, PDA cross linked AIE nanotheranostic systems can be easily prepared by design of AIE dyes and fabrication of AIE dyes and dopamine contained polymers. Photothermal treatment of cancer using PDA cross linked AIE nanotheranostic systems were further explored for the photothermal effects of PDA. On the other hand， many other moieties including functional polymers, therapeutics, targeting agents can be further introduced onto PDA cross linked AIE nanoparticles via Michael addition reaction due to the high reactivity of PDA, thus multifunctional nanotheranostic systems based on PDA cross linked AIE nanoparticles can be fabricated via mussel inspired chemistry. Then cell imaging, drug loading and controlled release as well as their targeting profiles of these multifunctional nanotheranostic systems will be investigated. Their pharmacokinetic behavior, biocompatibility as well as anti-tumor effects were also involved. The proposal developed a novel method for fabrication of PDA cross linked AIE based multifunctional theranostics. It will be not only of significance for deeply understanding the mussel inspired chemistry, but also provide novel ideas for development of other multifunctional nanotheranostic systems.