组织型纤溶酶原激活剂（t-PA）是临床上用于治疗血栓相关疾病的主要药物，其应用过程中的主要问题是半衰期短，采用药物包载和释放的方式是解决该问题的主要方法之一。本项目拟构建一种概念上全新的t-PA释放系统：巧妙利用t-PA和Plg（纤维蛋白溶酶原）与ε-赖氨酸之间亲和性的差异，使负载于ε-赖氨酸化载体上的t-PA在接触血液环境时被Plg替换而得以释放。课题拟在具有多孔结构的载体上构建上述t-PA释放系统，通过改变载体的多孔结构及化学组成控制Plg对t-PA的替换作用，从而调控t-PA释放速率。将系统研究载体结构和化学组成对t-PA的负载、释放以及活性的影响，并评价该t-PA释放系统的各方面生物性能。该系统可推广至多种形式的多孔载体上，如纳米药物载体或血管植入材料，从而实现其在t-PA溶栓治疗以及血液接触材料方面的应用。

Tissue-plasminogen activator (t-PA) is the main drug clinically used in the treatment of thrombotic diseases. The major issue in the therapeutic use of t-PA is its very short half-life in the circulation. Efforts have been made to overcome this deficiency by drug encapsulation and release. In the proposed research a new concept of t-PA releasing system based on the different affinities of t-PA and plasminogen to ε-lysine will be developed.In this system, t-PA is released from ε-lysine modified carriers into blood by plasminogen displacing. The t-PA releasing system will be constructed on the carriers with porous structure.By varying structure and chemistry of the carriers, t-PA releasing driven by plasminogen displacing could be regulated. Factors that affect the binding, releasing and activity preserving of t-PA, as well as biological properties of the system will be investigated. The system can be also constructed on other functional mateirals, such as porous nanoparticles and vascular grafts, and thus would be promising in therapeutic and blood-contact applications.