目的：将抗人CD40单克隆抗体5C11与3种含有不同反应基团的聚合胶束（polymeric micelle，PM）偶联，构建相应5C11偶联的聚合胶束（5C11 coupled polymeric micelle，PM-5C11），筛选出其中最适合与5C11偶联的PM，并观察该偶联物的生物学特性。方法：分别合成3种不同化学结构的聚合物材料，制备相应PM，与5C11偶联后制备PM-5C11，选择其中偶联率和生物安全性均较高的作为最适PM-5C11。将最适PM-5C11与人Burkitt淋巴瘤Daudi细胞株作用，观测其生物学活性及其被Daudi细胞摄取的能力。结果: 成功制备了分别含对甲苯磺酸酯基、丙烯基、羧基的3种PM，其中含对甲苯磺酸酯基和羧基的PM与5C11的偶联率均明显高于含丙烯基的PM的偶联率\[（28.08±2.24）%、（29.06±1.37）% vs （21.26±104）%，P<0.05\]；由于含羧基的PM在制备过程中易残留细胞毒性物质，故选取含对甲苯磺酸酯基的PM作为最适PM。相应的最适PM成功偶联5C11形成PM-5C11，最适PM-5C11显示出5C11原有的生物学活性，并且可被Daudi细胞摄取。结论：构建的3种PM中，含对甲苯磺酸酯基的PM在生物安全性、偶联率及相应PM-5C11的生物学活性方面最优，可作为构建纳米药物载体的最佳选择。

Objective:A human CD40 monoclonal antibody, 5C11, was coupled with three kinds of polymeric micelles (PMs) containing different chemical groups respectively to construct the corresponding 5C11 coupled polymeric micelles (PM-5C11). The optimal PM for coupling with 5C11 was selected among them, and evaluate its biological activity. Methods: Three kinds of copolymers with different chemical composition were synthesized respectively to prepare the corresponding PM and PM-5C11 after coupled with 5C11. The PM-5C11 which exhibited both higher coupling efficiency and greatest biological safety was selected to be the optimal one among them. The optimal PM-5C11 was then interacted with Daudi cell line, derived from human Burkitt lymphoma, to evaluate its biological activity and the cellular uptake by Daudi cells. Results: Three kinds of PMs containing tosyl group, allyl group or carboxyl group had been prepared successfully. The coupling efficiencies of 5C11 to PMs containing tosyl group or allyl group were both higher than that to PM containing carboxyl group (\[28.08±2.24\]%, \[29.06±137\]% vs \[21.26±1.04\]%, P<0.05). The PM containing tosyl group was chosen to be the optimal one because cytotoxic reagent remained during the preparation of the PM containing allyl group. The corresponding optimal PM coupled with 5C11 to form PM-5C11, which exhibited the original bioactivity of 5C11 and could be uptaken by Daudi cells. Conclusion: Among the three kinds of PMs, the PM containing tosyl group exhibits the best biological safety and the relative higher coupling efficiency; its corresponding PM-5C11 shows the best biological activity. This PM could be the best choice for constructing the nano-drug carrier.

国家自然科学基金资助项目（No．81101556）；江苏省普通高校研究生科研创新计划项目资助（No. CXZZ11_0110）；苏州市科技发展计划项目（No． SYSD2011084）