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轉(zhuǎn)鐵蛋白與細(xì)胞穿膜肽共修飾脂質(zhì)體抑制視網(wǎng)膜母細(xì)胞瘤的作用研究

發(fā)布時(shí)間:2018-03-10 17:14

  本文選題:轉(zhuǎn)鐵蛋白 切入點(diǎn):細(xì)胞穿膜肽 出處:《眼科新進(jìn)展》2015年05期  論文類型:期刊論文


【摘要】:目的采用薄膜分散法制備轉(zhuǎn)鐵蛋白(transferrin,TF)與細(xì)胞穿膜肽(transcriptional activator protein,TAT)共修飾載多西紫杉醇(docetaxel,DOC)脂質(zhì)體(TF/TAT-LP-DOC),探討其對(duì)視網(wǎng)膜母細(xì)胞瘤(HXO-RB44)的靶向治療作用。方法采用薄膜分散法制備TF/TAT-LP-DOC,并對(duì)其進(jìn)行表征。通過MTT實(shí)驗(yàn)考察脂質(zhì)體對(duì)HXO-RB44細(xì)胞的毒性,流式細(xì)胞儀檢測(cè)HXORB44細(xì)胞對(duì)不同脂質(zhì)體的攝取效率。構(gòu)建HXO-RB44細(xì)胞腫瘤球模型,研究TF/TAT-LP-DOC對(duì)實(shí)體腫瘤的生長抑制作用。結(jié)果所制備的TF/TATLP-DOC粒徑為(115.8±8.5)nm,Zeta電位為(23.58±3.65)m V,DOC的包封率為85.8%。MTT檢測(cè)結(jié)果顯示,LP-DOC、TFLP-DOC、TATLP-DOC和TF/TATLP-DOC組HXO-RB44細(xì)胞存活率分別為66.5%、43.6%、39.4%和18.9%,差異有統(tǒng)計(jì)學(xué)意義(P0.01)。與LP-DOC、TFLP-DOC和TATLP-DOC組比較,TF/TATLP-DOC組的腫瘤細(xì)胞存活率顯著低于其他脂質(zhì)體組,差異均有統(tǒng)計(jì)學(xué)意義(均為P0.01)。TF/TATLP-DOC組細(xì)胞存活率隨時(shí)間的延長而降低,差異有統(tǒng)計(jì)學(xué)意義(P0.01)。HXO-RB44細(xì)胞對(duì)TF/TATLP的攝取效率分別是TFLP、TATLP和LP的2.65倍、2.32倍和3.86倍,差異均有統(tǒng)計(jì)學(xué)意義(均為P0.01)。TFLP和TATLP的細(xì)胞攝取效率高于LP,差異均有統(tǒng)計(jì)學(xué)意義(均為P0.01)。相同脂質(zhì)體在4 h的攝取效率高于2 h,差異有統(tǒng)計(jì)學(xué)意義(P0.01)。給藥7 d后,生理鹽水組腫瘤球持續(xù)生長,體積增大1.44倍,LPDOC組腫瘤球體積增大到原體積的1.14倍,TF/TAT-LP-DOC組、TATLP-DOC組和TFLP-DOC組腫瘤球體積減小到原體積的35%、62%和58%,與LP-DOC、TFLP-DOC和TATLP-DOC組比較,TF/TATLP-DO組腫瘤球體積顯著小于其他脂質(zhì)體組,差異均有統(tǒng)計(jì)學(xué)意義(均為P0.01)。腫瘤球體積隨著時(shí)間的延長而減小,差異有統(tǒng)計(jì)學(xué)意義(P0.01)。結(jié)論 TF/TATLP-DOC制備工藝簡單,與HXO-RB44細(xì)胞具有良好的親和性,是一種潛在高效的腫瘤靶向給藥系統(tǒng)。
[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 鹵8.5nmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmnmct, the entrapment efficiency of TF/TATLP-DOC was 85.8 鹵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.
【作者單位】: 南陽市中心醫(yī)院眼科;
【分類號(hào)】:R739.7

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