中文摘要：

目的 研究人鼠嵌合抗肿瘤细胞核单抗（chTNT-3）-空间稳定脂质体的制备方法、免疫活性及体外靶向性。方法 合成聚乙二醇末端带吡啶二硫丙酰基的磷脂衍生物（PDP—PEG—HSPE），制备含PDP—PEG—HSPE的空间稳定脂质体，经二巯基苏糖醇还原后共价连接马来酰亚胺衍生化抗体。荧光胺法和钼蓝法测定脂质体与抗体的连接效率及抗体密度，激光散射粒度仪测定其粒径分布，ELISA法检测脂质体表面的抗体免疫活性。体外实验考察该免疫脂质体与固定Raji细胞的结合活性。结果chTNT-3-空间稳定脂质体的粒径分布为（115±33）nm。当初始Ab／PDP-PEG-HSPE=1：10时，脂质体与抗体的连接效率为71％，抗体密度为106μg Ab/μmol PL。chTNT-3经化学修饰后连接到脂质体表面，其免疫活性基本保留。chTNT-3-空间稳定脂质体能特异性地结合固定Raji细胞。结论通过PDP-PEG-HSPE法共价连接抗体制备的chTNT-3-空间稳定脂质体能基本保留chTNT-3的免疫活性，具有体外靶向细胞核抗原的能力。

英文摘要：

Aim To prepare sterically stabilized liposomes modified with chimeric TNT-3 monoclonal antibody （chTNT-3） and investigate their immunoreactivity and in vitro targeting. Methods An endgroup functionalized polyethylene glycol-lipid derivative （pyridylthiopropionoylamino-polyethylene glycolhydrogenated soy phosphatidylethanolamine, PDP-PEG-HSPE ） was synthesized and incorporated to sterically stabilized liposomes. After mild thiolysis of the PDP groups by dithiothreitol, liposomes were covalently linked with maleimide-derivatized chTNT-3 and formed sterically stabilized immunoliposomes. Coupling efficiency, antibody density, size distribution, immunoreactivity of chTNT-3-modified sterically stabilized liposomes （chTNT-3-SLs） and specific binding properties of the chTNT-3-SLs to fixed Raji cells were determined, separately. Results Higher initial Ab/PDP-PEG-HSPE molar ratios resulted in higher antibody density on the surface of liposomes but lower coupling efficiency. The optimal coupling efficiency of 71% was obtained while antibody density in liposome was 106 μg antibody/μmol phospholipids （as initial antibody/PDP-PEG-HSPE = 1： 10）. The chTNT-3-SLs had a narrow size distribution after extrusion and the mean size of this immunoliposomes was （115 ± 33） nm. The immunoreactivity of chTNT-3 can be preserved after efficient attachment of maleimide-derivatized chTNT-3 to the surface of liposomes. But calculated per antibody concentration, the immunoreactivity of chTNT-3-SLs would obviously decrease compared to that of chTNT-3 or chTNT-3 derivatives. Significantly higher binding of chTNT-3-SLs to fixed Raji cells directed by chTNT-3 was obtained compared to other preparations in serial dilutions （P 〈 0.01）. Conclusion chTNT-3-SLs prepared by PDP-PEG-HSPE method remained most immunoreactivity of chTNT-3 and was able to bind nuclear antigens in vitro.