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OALib Journal期刊
ISSN: 2333-9721
费用：99美元
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具有穿膜功能的嵌合型avpi-低分子量鱼精蛋白/dna共给药系统的抗肿瘤研究
, PP. 1718-1723
Keywords: 穿膜肽,凋亡肽,基因给药,细胞凋亡,trail,avpi,肿瘤治疗
Abstract:
本文旨在合成具有穿膜活性的促凋亡avpi-低分子量鱼精蛋白嵌合多肽(avpi-lmwp),制备安全有效的avpi-lmwp/ptrail基因共给药系统,通过凋亡肽avpi与肿瘤坏死因子相关凋亡诱导配体基因(ptrail)联合用药来发挥抗肿瘤作用.采用标准固相合成法合成嵌合型多肽avpi-lmwp.基于静电吸附作用,avpi-lmwp可与dna药物形成avpi-lmwp/ptrail复合物,并对其理化性质进行了表征,同时研究其细胞摄取效率和抗肿瘤增殖能力.结果表明,采用共孵育法成功制备了avpi-lmwp/ptrail复合物,随着avpi-lmwp/ptrail质量比的增加,复合物的平均粒径逐渐减小,zeta-电位变化较小.凝胶电泳实验结果表明,当两者质量比大于15:1时,avpi-lmwp能完全包裹和压缩质粒ptrail.体外细胞摄取实验显示,随着二者质量比的增加,细胞摄取效率有所提高.体外细胞毒性实验表明,avpi-lmwp/ptrail(w:w=20:1)复合物抑制hela细胞增殖的效果显著强于ptrail、avpi-lmwp及lmwp/ptaril复合物.研究显示,avpi-lmwp/ptrail基因共给药系统能将质粒高效递送到hela细胞内,并能有效地诱导肿瘤细胞凋亡,是具有联合治疗应用价值的多肽/基因共给药系统.
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