论文部分内容阅读
通过制备pH敏感穿膜肽TH[AGYLLGHINLHHLAHL(Aib)HHIL-Cys]修饰的载免疫佐剂α-半乳糖神经酰胺的脂质体(TH modified liposome loaded with alpha-galactosylceramides,αGC-TH-Lip),并研究其对荷瘤小鼠免疫功能的影响及其作用机制。采用薄膜分散-探头超声法制备脂质体,测定TH修饰的脂质体(TH peptidemodified liposome,TH-Lip)体外被小鼠树突状细胞(dendritic cell,DC)系DC2.4细胞的摄取;给药后荷瘤小鼠体内抗肿瘤相关免疫细胞的激活、促进DC细胞成熟的程度以及辅助性T细胞(helper T cell,Th)的分化情况。结果显示,TH-Lip在体外被DC2.4细胞的摄取量是聚乙二醇修饰的脂质体(polyethylene glycols modified liposome,PEG-Lip)的1.48倍;给药后荷瘤小鼠体内自然杀伤性T细胞、自然杀伤细胞和巨噬细胞数量分别为(0.43±0.048)%、(12.80±0.50)%和(3.13±0.26)%,成熟DC细胞达到(2.30±0.22)%,细胞毒性T淋巴细胞的数量达到(32.30±0.80)%,较游离αGC组有显著性差异;αGC-TH-Lip对Th1细胞分化的诱导效应最强,对Th2细胞的分化无明显促进作用。此结果表明,该αGC-TH-Lip能够提高小鼠的免疫活性,增强α-半乳糖神经酰胺的作用效果,促进淋巴细胞更多地向细胞免疫的方向分化,从而达到更好的抗癌免疫治疗作用。
The TH modified liposome loaded with alpha-galactosylceramides (αGC-TH-Lip) was prepared by preparing the pH sensitive transmembrane peptide TH [AGYLLGHINLHHLAHL (Aib) HHIL-Cys] And study its effect on the immune function of tumor-bearing mice and its mechanism of action. Liposomes were prepared by thin-film dispersive-probe ultrasound and the ingestion of TH-liposomes by dendritic cells (DCs) DC2.4 cells in vitro was measured. Activation of anti-tumor related immune cells in tumor-bearing mice after administration, the degree of promoting DC cell maturation and the differentiation of helper T cell (Th). The results showed that the uptake quantity of TH-Lip by DC2.4 cells in vitro was 1.48 times higher than that of polyethylene glycol modified liposomes (PEG-Lip) (0.43 ± 0.048)%, (12.80 ± 0.50)% and (3.13 ± 0.26)%, respectively. The number of mature T cells, natural killer cells and macrophages reached 2.30 ± 0.22% The number of cells reached (32.30 ± 0.80)%, which was significantly different from that of free αGC group. ΑGC-TH-Lip had the strongest induction effect on Th1 cell differentiation but had no obvious promotion on the differentiation of Th2 cells. The results showed that the αGC-TH-Lip can enhance the immunological activity of mice and enhance the effect of α-galactosylceramide, and promote the lymphocyte to differentiate more towards cellular immunity so as to achieve better anti-cancer immunity Therapeutic effect.