可靶、可视、可控的血小板载药系统的设计及其抗淋巴瘤效应的研究

恶性淋巴瘤分子靶向治疗是目前研究的热点。B细胞系恶性淋巴瘤细胞膜表面高表达CD22抗原，与CD20不同，CD22抗原与抗体结合后能迅速内化。我们前期研究结果显示以血小板作为药物载体的载药量远高于一般纳米载体。本研究拟在前期基础上构建一种新型血小板主动靶向载药体系：1. 在血小板表面修饰CD22抗体(Fab’)片段，即能实现主动靶向性，又可避免抗体Fc段介导的吞噬细胞的吞噬作用，使血循环中的载药血小板寿命延长至正常生理9 天左右；2.通过不断优化CD22(Fab’)片段、DOX、血小板的装载条件，制备出可靶、可视、可控的载药体系CD22(Fab’)-血小板-DOX；3. 观察其对淋巴瘤Raji细胞及动物模型的靶向治疗作用，同时对其药代动力学、生物相容性及体内分布机制进行深入的研究，为临床淋巴瘤靶向治疗提供有力依据。

More attention has been focused on the targetd therapy of lymphoma.CD22 antigen was found to be highly expressed on the surface of lymphoma cell in many studies. Compared with nano-biotechnology, platelets which are used as carrier of anti-lymphoma drug (DOX) as delivery of drug to the targeted site an essential blood component having a natural affinity for cancer cells, can achieve higher loading efficiency, more efficient biocompatibility and better targeted. Our initial studies have proved that DOX was nicely combined with platelets to construct platelets-DOX for drug delivery system with the loading efficiency of 50.08±2.36%, which was pH sensitive. In this study, a new type active targeted delivery system was presented to target lymphoma cells: (1) we will construct CD22-platelet-DOX which is a new drug delivery system with active targeted ability and pH sensitive, by optimizing the reactive conditions of CD22Ab, DOX and platelets; (2) The targeted anti-tumor ability against types of lymphomas cells and animals will be observed. Biocompatibility, pharmacokinetic and distribution will also be studied at the same time. CD22Ab-Platelet-DOX will be an effective approach to the clinic targeted therapy of lymphoma.