粒毛盘菌YM405胞外多糖硒纳米颗粒的制备及其抗肿瘤活性

Preparation and anticancer activity of Lachnum YM405 extracellular polysaccharide-selenium nanoparticles

文章研制一种粒毛盘菌YM405胞外多糖LEP-2b-硒纳米颗粒(LEP2b-SeNPs),发现LEP-2b的质量浓度影响SeNPs的粒径,LEP2b-SeNPs在透射电子显微镜(transmission electron microscope,TEM)下分散,发现粒径比SeNPs的小,且具有更高的稳定性,注射LEP2b-SeNPs不会对正常小鼠的体质量造成明显影响,说明小鼠对LEP2b-SeNPs的剂量具有良好的耐受性。建立H22荷瘤小鼠模型,研究LEP2b-SeNPs的抗肿瘤活性,低剂量LEP2b-SeNPs和阳性药物组的小鼠瘤质量与模型组相比差异极其显著(P<0.001),模型组小鼠体质量比正常组大,食物摄入量随天数明显下降;而LEP2b-SeNPs处理组的小鼠体质量和食物摄入量相对稳定,表明LEP2b-SeNPs有较高的抗肿瘤活性。免疫组化结果表明,低剂量LEP2b-SeNPs抑制了肿瘤组织中Ki-67的表达(P<0.01),其效果比高剂量LEP2b-SeNPs更显著(P<0.05),说明低剂量LEP2b-SeNPs有效抑制了肿瘤细胞增殖。生化指标检测结果表明,LEP2b-SeNPs处理使荷瘤小鼠血清中γ-干扰素(IFN-γ)、白细胞介素-1β(IL-1β)、白细胞介素-2(IL-2)、肿瘤坏死因子-α(TNF-α)、谷草转氢酶(AST)和碱性磷酸酶(AKP)的水平明显升高(P<0.05或P<0.01),肝脏过氧化氢酶(CAT)水平上升,而丙二醛(MDA)水平降低,表明LEP2b-SeNPs能够显著减轻荷瘤小鼠的氧化应激。

In this paper,the Lachnum YM405 extracellular polysaccharide LEP-2b-SeNPs nanoparticles(LEP2b-SeNPs)were prepared.It was found that the concentration of LEP-2b affects the particle size of SeNPs.LEP2b-SeNPs were dispersed under transmission electron microscope(TEM)and the particle size was smaller than that of SeNPs,showing higher stability.The injection of LEP2b-SeNPs did not significantly reduce the body weight of normal mice,indicating that the mice had a good tolerance to the dose of LEP2b-SeNPs.The H22 tumor-bearing mice model was established to study the antitumor activity of LEP2b-SeNPs.Compared with the model group,the tumor weight of mice in the low-dose LEP2b-SeNPs and positive control groups was extremely significant(P<0.001).The mice of model group had larger body weight than the normal group,and the food intake decreased obviously with days,while the body weight and food intake of LEP2b-SeNPs-treated mice were relatively stable,indicating that LEP2b-SeNPs had excellent antitumor activity.Immunohistochemical assay results demonstrated that the low-dose LEP2b-SeNPs inhibited the expression of Ki-67 in tumor tissues(P<0.01),and its effect was more significant than that with the high-dose LEP2b-SeNPs(P<0.05),which indicated that the low-dose LEP2b-SeNPs effectively suppressed cancer cell proliferation.The results of biochemical indicators showed that LEP2b-SeNPs treatment markedly increased the levels of IFN-γ,IL-1β,IL-2,TNF-α,AST and AKP in the serum of tumor-bearing mice(P<0.05 or P<0.01),elevated the liver CAT level,but decreased the liver MDA level,indicating that LEP2b-SeNPs can significantly reduce oxidative stress in tumor-bearing mice.