聚多巴胺多功能纳米药物输运体系的构筑及药效评价

发展安全高效的多功能性纳米药物输运体系是当今纳米生物医学研究的热点和前沿领域。申请人以前期在纳米生物医学和贻贝仿生化学领域的研究工作为基础，提出了构建基于聚多巴胺荧光纳米颗粒的多功能纳米药物输运体系的研究思路。通过多巴胺的氧化自聚和聚多巴胺的高反应活性,制备具有荧光的聚多巴胺纳米颗粒并将多种功能性组分包括治疗性成分（细胞色素C、未甲基化寡聚脱氧核苷序列），靶向成分(穿膜肽、抗体)以及其它功能性成分（聚乙二醇等功能性高分子）等通过Michael加成反应连接到聚多巴荧光纳米颗粒的表面。研究聚多巴胺多功能纳米颗粒的细胞成像、药物载带和控制释放以及靶向性能,进而考察其代谢动力学行为、生物安全性以及抗肿瘤效果。本项目提出了一种全新的构筑基于聚多巴胺纳米颗粒多功能药物输运体系的方法；对于深入理解贻贝仿生化学具有重要意义，同时也为发展其它多功能纳米药物输运体系提供了新的研究思路。

The development of safe, efficient and multifunctional drug delivery systems is one of the frontier and hot research field in nanomedicine.Based on our research background in nanomedicine and mussel-inspired chemistry; we proposed the ideas for fabrication of multifunctional drug delivery systems based on the fluorescent polydopamine (PDA) nanoparticles. Take advantage of the self-polymerization of dopamine under alkaline solution, fluorescent PDA nanoparticles can be facily prepared.On the other hand, many functional moieties including the therapeutics (Cytochrome C, CPG oligodeoxynucleotides); targeting agents (cell-penetrating peptides, antibodies) and functional polymers such as polyethylene glycol （PEG） et al could be further introduced onto PDA nanoparticles through Michael addition reaction due to the high reactivity of PDA nanoparticles. Then the cell imaging, drug loading and controlled release as well as their targeting profiles of these multifunctional drug delivery 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 nanoparticle based multifunctional drug delivery systems. It will be not only of significance for deeply understanding the mussel-inspired chemistry, but also provide novel ideas for development of other multifunctional drug delivery systems.