靶向树突状细胞表面分子DEC-205长循环免疫脂质体稳定性模型的构建及其生物学特性

Stability model construction of long-circulating immunoliposome targeting to dendritic cell surface molecule DEC-205 and analysis of its biological charac teristics

应用多相分散体系的动力稳定性和聚结稳定性理论,以薄膜分散法构建了靶向树突状细胞(dendritic cells,DCs)表面分子DEC-205长循环免疫脂质体(anti-DEC-205 iLPSM)的稳定性模型,并对其物理稳定性、生物学特性等进行了考察。结果表明经优化后的脂质体4℃贮存7d后粒径分布变化较小;FITC-dextran累积泄漏率小于7%;耦联抗DEC-205的免疫脂质体(anti-DEC-205 iLPSM)可特异性地识别DCs,并作为良好载体将FITC-dextran带入DCs浆内。anti-DEC-205 iLPSM模型的构建为进一步研究抗原靶向DEC-205受体后的体内免疫应答情况提供了工作基础,有望开发一种新型DCs疫苗应用于临床。

To enable the liposome to deliver encapsulated drugs or antigen to dendritic cells efficiently and induce strong T cell immune response or specific immune tolerance, the hposomes containing FTTC- dextran were prepared by film dispersion; DSPE- PEG（2000） was used to modify the liposome membrane so that it has a long circulatory function; SPDP, heterotypic Dual-functional crosslinker, was used to conjugate the mouse DEC- 205 antibodies to the hposomes so that the modified liposomes could target DCs. The optimized liposomes showed stable physicochemical properties when stored at 4℃ for 7 days. Under this condition, liposome size and size distribution did not noticeably change. Cumulative leakage rate of FTTC - dextran from liposomes was less than 7 %. Anti - DEC - 205 - immunoliposomes （ anti - DEC - 205 iLPSM）, as drug carriers, can specifically recognize dendritic cells and dehver FTTC - dextran into the cytoplasm. The construction of an anti - DEC - 205 iLPSM model lays solid foundations for further work researching immune response after antigen targeting to DEC - 205 receptors in vivo. Anti - DEC - 205 iLPSM could become a new type of DC vaccine.