转铁蛋白与细胞穿膜肽共修饰脂质体抑制视网膜母细胞瘤的作用研究

发布时间：2018-03-10 17:14

本文选题：转铁蛋白　切入点：细胞穿膜肽　出处：《眼科新进展》2015年05期 　论文类型：期刊论文

【摘要】：目的采用薄膜分散法制备转铁蛋白(transferrin,TF)与细胞穿膜肽(transcriptional activator protein,TAT)共修饰载多西紫杉醇(docetaxel,DOC)脂质体(TF/TAT-LP-DOC),探讨其对视网膜母细胞瘤(HXO-RB44)的靶向治疗作用。方法采用薄膜分散法制备TF/TAT-LP-DOC,并对其进行表征。通过MTT实验考察脂质体对HXO-RB44细胞的毒性,流式细胞仪检测HXORB44细胞对不同脂质体的摄取效率。构建HXO-RB44细胞肿瘤球模型,研究TF/TAT-LP-DOC对实体肿瘤的生长抑制作用。结果所制备的TF/TATLP-DOC粒径为(115.8±8.5)nm,Zeta电位为(23.58±3.65)m V,DOC的包封率为85.8%。MTT检测结果显示,LP-DOC、TFLP-DOC、TATLP-DOC和TF/TATLP-DOC组HXO-RB44细胞存活率分别为66.5%、43.6%、39.4%和18.9%,差异有统计学意义(P0.01)。与LP-DOC、TFLP-DOC和TATLP-DOC组比较,TF/TATLP-DOC组的肿瘤细胞存活率显著低于其他脂质体组,差异均有统计学意义(均为P0.01)。TF/TATLP-DOC组细胞存活率随时间的延长而降低,差异有统计学意义(P0.01)。HXO-RB44细胞对TF/TATLP的摄取效率分别是TFLP、TATLP和LP的2.65倍、2.32倍和3.86倍,差异均有统计学意义(均为P0.01)。TFLP和TATLP的细胞摄取效率高于LP,差异均有统计学意义(均为P0.01)。相同脂质体在4 h的摄取效率高于2 h,差异有统计学意义(P0.01)。给药7 d后,生理盐水组肿瘤球持续生长,体积增大1.44倍,LPDOC组肿瘤球体积增大到原体积的1.14倍,TF/TAT-LP-DOC组、TATLP-DOC组和TFLP-DOC组肿瘤球体积减小到原体积的35%、62%和58%,与LP-DOC、TFLP-DOC和TATLP-DOC组比较,TF/TATLP-DO组肿瘤球体积显著小于其他脂质体组,差异均有统计学意义(均为P0.01)。肿瘤球体积随着时间的延长而减小,差异有统计学意义(P0.01)。结论 TF/TATLP-DOC制备工艺简单,与HXO-RB44细胞具有良好的亲和性,是一种潜在高效的肿瘤靶向给药系统。
[Abstract]:Objective to study the targeted therapeutic effect of transferrin transferrin TFT and transcriptional activator protein tact (TAT) on retinoblastoma by co-modification of docetaxel doc liposome (TFP / TAT-LP-DOCN). Methods the method of membrane dispersion was used to prepare RB44. Methods the method of membrane dispersion was used to prepare TGF- / TAT-LP-DOC4. Methods the method of membrane dispersion was used to prepare the liposome of TFP / TAT-LP-DOCN. Methods the method of membrane dispersion was used to prepare RB44. TFR / TAT-LP-DOC was characterized. The toxicity of liposomes to HXO-RB44 cells was investigated by MTT assay. Flow cytometry was used to detect the uptake efficiency of different liposomes in HXORB44 cells. A tumor ball model of HXO-RB44 cells was established. To study the inhibitory effect of TF/TAT-LP-DOC on the growth of solid tumor. Results the diameter of TF/TATLP-DOC was 115.8 卤8.5nmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmct, the entrapment efficiency of TF/TATLP-DOC was 85.8 卤3.65mVDOC. The results showed that the survival rate of HXO-RB44 cells in TFLP-DOCnTP-DOC and TF/TATLP-DOC groups was 66.5@@. The survival rate of tumor cells in TFLP-DOC group was significantly lower than that in other liposome groups, compared with that in TATLP-DOC group, and the survival rate of tumor cells in TFP / TATLP-DOC group was significantly lower than that in other liposome groups. The cell survival rate of P0.01U. TF- / TATLP-DOC group decreased with the prolongation of time, and the uptake efficiency of TF/TATLP was 2.65 times, 2.32 times and 3.86 times of that of TFLPTATLP and LP, respectively. The cell uptake efficiency of both P0.01U. TFLP and TATLP was significantly higher than that of LP.The uptake efficiency of the same liposome was higher than that of LP0.01L at 4 h, and the difference was statistically significant after 7 days of administration. In saline group, tumor balls continued to grow, The volume of tumor ball increased to 1.14 times of the original volume in 1.44 times of LPDOC group. The volume of tumor ball in TFP-TAT-LP-DOC group and TFLP-DOC group decreased to 35% and 58% of the original volume. Compared with LP-DOCU TFLP-DOC group and TATLP-DOC group, the volume of tumor ball in TFP-TATLP-DO group was significantly lower than that in other liposomes group. The volume of tumor spheres decreased with time, and the difference was statistically significant (P 0.01). Conclusion the preparation process of TF/TATLP-DOC is simple, and it has good affinity with HXO-RB44 cells. It is a potentially efficient tumor targeting drug delivery system.
【作者单位】：南阳市中心医院眼科;
【分类号】：R739.7

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