pH敏感穿膜肽修饰的载α-半乳糖神经酰胺的脂质体免疫作用机制的初步研究

发布时间：2018-07-13 17:36

【摘要】：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。
[Abstract]:The pH sensitive peptide th (AGYLGHINLHHL HLAHHIL-Cys) modified 伪 -galactosyl ceramides (伪 GC-TH-Lip) was prepared and its effect on the immune function of tumor-bearing mice was studied. Liposomes were prepared by thin-film dispersion-probe ultrasound method, and the uptake of th peptidemodified liposome-TH-Lip by dendritic cell line DC2.4 cells was measured in vitro, and the activation of anti-tumor related immune cells in tumor-bearing mice after administration of TH-modified liposome (th peptidemodified Liposome-TH-Lip) was measured. Promote the degree of DC cell maturation and the differentiation of helper T cell Th. The results showed that the uptake of TH-Lip by DC2.4 cells was 1.48 times higher than that of (polyethylene glycols modified liposome PEG-Lip modified by polyethylene glycol in vitro. The number of natural killer cells and macrophages were (0.43 卤0.048), (12.80 卤0.50)% and (3.13 卤0.26), respectively. The number of mature DC cells was (2.30 卤0.22) and the number of cytotoxic T lymphocytes was (32.30 卤0.80). The differentiation of Th2 cells was not promoted. The results showed that the 伪 -GC-TH-Lip could increase the immune activity of mice, enhance the effect of 伪 -galactose-ceramide, and promote the differentiation of lymphocytes into cellular immunity, thus achieving a better anti-cancer immunotherapy effect.
【作者单位】：四川大学华西药学院靶向药物与传递系统教育部重点实验室;
【基金】：国家自然科学基金重大项目(81690261)
【分类号】：R943

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