透明质酸修饰载紫杉醇靶向脂质体抑制脑肿瘤干细胞的初步评价

Primary evaluation on inhibiting effects of hyaluronic acid modified paclitaxel loaded liposome against brain tumor stem cells

目的:制备透明质酸修饰载紫杉醇(paclitaxel,PTX)靶向脂质体(HALP-PTX),考察其对脑胶质瘤肿瘤干细胞的亲和力和抑制效果。方法:采用薄膜分散法制备HALP-PTX,细胞摄取实验研究胶质瘤干细胞对脂质体的摄取。MTT实验研究不同紫杉醇药物对肿瘤干细胞的增殖抑制率。构建原位移植瘤动物模型,考查不同脂质体对荷瘤裸鼠的生存期的影响。结果:肿瘤干细胞对HALP的摄取能力显著大于普通脂质体(LP),脑肿瘤干细胞对经透明质酸修饰的脂质体的摄取效率是普通脂质体的2.8倍,差异有统计学意义(P<0.01);HALP-PTX对肿瘤干细胞的生长的抑制作用显著强于LP-PTX,HALPPTX能够显著延长荷瘤裸鼠的中位生存期,生理盐水组、PTX组、LP-PTX组和HALP-PTX组的中位生存期分别为19,23,29,41 d。结论:与PTX以及LP-PTX相比,HALP-PTX能够更加有效的被脑肿瘤干细胞识别和摄取,抑制肿瘤细胞的增殖,具有更强的抗肿瘤作用。

OBJECTIVE To prepare hyaluronic acid conjugated paclitaxel loaded liposome and evaluate the efficiency of cellular uptake and the inhibiting effects against brain cancer stem cells. METHODS Liposome was prepared by film-ultrasonic method. Cellular uptake by brain tumor stem cell was explored. The anti-proliferation efficiency of HALP-PTX was evaluated by MTT assay. Brain tumor stem cells were used to build orthotopic tumor model, which was used to evaluate the anti-cancer effects. RESULTS The uptake efficiency of HALP was 2. 8 times higher than that of LP （P〈0. 01）. The anti-proliferative activity against brain tumor stem cell confirmed strong inhibitory effects of HALP-PTX. HALP-PTX could significantly prolong median survival of nude rats. The median survival of nude rats in saline, PTX, LP-PTX and HALP-PTX groups were 19, 23, 29 d and 41 d. CONCLUSION Comparing with PTX and LP-PTX, HALP-PTX can more persistently inhibit the proliferation of brain tumor stem cells. Therefore, as a new nanometer drug, HALP-PTX has a special applying value for therapy of brain tumor.