PLGA缓释纳米微球肿瘤疫苗防治结肠癌的实验研究

Experimental study of sustained-release PLGA nanoparticle vaccine in colorectal cancer

制备并探讨PLGA缓释纳米微球肿瘤疫苗对小鼠结肠癌的防治作用及机制。用双乳化法制备了一种以小鼠结肠癌细胞CMT93为抗原,以纳米材料PLGA为载体,辅以粒细胞-巨噬细胞集落刺激因子(GM-CSF)的新型缓释纳米微球肿瘤疫苗。体内试验表明,对于接种了结肠癌细胞的C57BL/6小鼠而言,提前接种新型缓释纳米微球肿瘤疫苗可使小鼠的成瘤率从100%降低至20%。而在C57BL/6小鼠结肠癌模型中,与对照相比,该新型缓释纳米微球肿瘤疫苗处理组的IFN-γ分泌水平最高,NK细胞和CTL细胞的杀伤活性最强,并且能特异性杀伤CMT93细胞,该杀伤活性能被抗CD8抗体阻断但不能被抗CD4抗体阻断。据此,本研究成功制备了一种对小鼠结肠癌具有良好的防治作用新型缓释纳米微球肿瘤疫苗。

We set to prepare a sustained-release PLGA nanoparticle vaccine for prevention and treatment of colorectal cancer in mice and explore its mechanism. A new kind of sustained-release nanoparticle tumor vaccine was generated by double emulsion method, with mice colorectal cancer cell CMT93 as antigen, nanomaterial PLGA as vector and granulocyte-macrophage-colony stimulating factor （GM-CSF） as assistant. For the C57BL/6 mice which were inoculated with colorectal cancer cells, the inocu- lation of this new sustained-release nanoparticle tumor vaccine could reduce the tumor formulation rate from 100% to 20%. On the other hand, in the C57BL/6 mouse model of colorectal cancer, the IFN-ν secretion level of vaccine-inoculated group was significantly higher than those of the other groups. And NK cells and CTL cells of the vaccineinoculated group had the strongest cytotoxic activity to specifically killing CMT93 cells and these activities could be blocked by anti-CD8 antibody but not by anti-CD4 antibody. Finally, a new kind of sustainedrelease PLGA nanoparticle vaccine was successfully prepared and provided to have good preventive and antitumor effect.