抗VEGF单克隆抗体偶联5-FU纳米微粒的初步研究

目的： 为了提高5-氟尿嘧啶(5-fluorouracil, 5-FU)的抗癌活性，采用抗VEGF单克隆抗体与 5-FU 聚乳酸纳米微粒交联结合制备具有靶向功能的免疫纳米微粒。 方法： 采用抗VEGF单克隆抗体与已制备的 5-FU 聚乳酸纳米微粒(5-FU-NPs)以化学键偶联连接的方法制备具有靶向功能的5-FU免疫纳米微粒(5-FU-Ab-NPs)，考察其形貌、粒径分布、体外释放和免疫活性等性能。结果： 5-FU-Ab-NPs仍呈规则球形，粒径约为（202±23）nm，体外释放实验表明该5-FU-Ab-NPs与5-FU-NPs具有相似缓释特性，免疫学检测和电镜检视显示偶联后的抗VEGF单克隆抗体免疫活性保持原活性的80%以上。结论： 5-FU-Ab-NPs保持原5-FU-NPs缓释药物的特点，具有双重活性功能，即免疫导向和缓释药物,有利于提高肿瘤局部药物浓度。

The anti VEGF monoclonal antibody conjugated with nanometer particle of 5-FU

AIM:The characteristics of nanometer particles, which were prepared by the conjugation of anti-VEGF monoclonal antibodies and 5-fluorouracil-loaded polylactic acid nanometer particles (5-FU-NPs), were investigated for improving the anticancer activity of 5-FU. METHODS:The method of couple linkage of chemical bonds was used to prepare the 5-FU-NPs with VEGF antibody, then the appearance, distribution of particle diameter, releasing in vitro and the immunological activity were detected. RESULTS:The 5-FU-Ab-NPs appeared as regular globular, the average particle diameter was (202±23)nm. The 5-FU-Ab-NPs possessed the similar delayed release character of 5-FUs. More than 80% of the immmunogical activity were detected in conjugates-retained antibody by the immunological methods and electron microscopy. CONCLUSION:The 5-FU-Ab-NPs possess the similar delayed released activity to 5-FU-NPs and have double activity of immune targeting and delayed releasing, which may increase the local concentration of 5-FU.