發(fā)布時間：2018-07-13 17:36

【摘要】：通過制備pH敏感穿膜肽TH[AGYLLGHINLHHLAHL(Aib)HHIL-Cys]修飾的載免疫佐劑α-半乳糖神經(jīng)酰胺的脂質(zhì)體(TH modified liposome loaded with alpha-galactosylceramides,αGC-TH-Lip),并研究其對荷瘤小鼠免疫功能的影響及其作用機制。采用薄膜分散-探頭超聲法制備脂質(zhì)體,測定TH修飾的脂質(zhì)體(TH peptidemodified liposome,TH-Lip)體外被小鼠樹突狀細胞(dendritic cell,DC)系DC2.4細胞的攝取;給藥后荷瘤小鼠體內(nèi)抗腫瘤相關(guān)免疫細胞的激活、促進DC細胞成熟的程度以及輔助性T細胞(helper T cell,Th)的分化情況。結(jié)果顯示,TH-Lip在體外被DC2.4細胞的攝取量是聚乙二醇修飾的脂質(zhì)體(polyethylene glycols modified liposome,PEG-Lip)的1.48倍;給藥后荷瘤小鼠體內(nèi)自然殺傷性T細胞、自然殺傷細胞和巨噬細胞數(shù)量分別為(0.43±0.048)%、(12.80±0.50)%和(3.13±0.26)%,成熟DC細胞達到(2.30±0.22)%,細胞毒性T淋巴細胞的數(shù)量達到(32.30±0.80)%,較游離αGC組有顯著性差異;αGC-TH-Lip對Th1細胞分化的誘導(dǎo)效應(yīng)最強,對Th2細胞的分化無明顯促進作用。此結(jié)果表明,該αGC-TH-Lip能夠提高小鼠的免疫活性,增強α-半乳糖神經(jīng)酰胺的作用效果,促進淋巴細胞更多地向細胞免疫的方向分化,從而達到更好的抗癌免疫治療作用。
[Abstract]:The pH sensitive peptide th (AGYLGHINLHHL HLAHHIL-Cys) modified 偽 -galactosyl ceramides (偽 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 鹵0.048), (12.80 鹵0.50)% and (3.13 鹵0.26), respectively. The number of mature DC cells was (2.30 鹵0.22) and the number of cytotoxic T lymphocytes was (32.30 鹵0.80). The differentiation of Th2 cells was not promoted. The results showed that the 偽 -GC-TH-Lip could increase the immune activity of mice, enhance the effect of 偽 -galactose-ceramide, and promote the differentiation of lymphocytes into cellular immunity, thus achieving a better anti-cancer immunotherapy effect.
【作者單位】： 四川大學(xué)華西藥學(xué)院靶向藥物與傳遞系統(tǒng)教育部重點實驗室;
【基金】：國家自然科學(xué)基金重大項目(81690261)
【分類號】：R943

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