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pH敏感性的TAT肽修饰胶束的制备及其体外评价 被引量:13

Preparation and in vitro evaluation of pH-sensitive TAT peptide conjugated micelles
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摘要 本文采用具有pH敏感性的硬脂酰磺胺甲氧嘧啶、mPEG2000-DOPE和TAT肽(transactivator of transcription peptide)修饰的聚乙二醇化磷脂,以薄膜分散法制备了载阿霉素的聚合物胶束。pH敏感胶束在pH 7.4的粒径约为20 nm,阿霉素的包封率为(99.1±2.1)%。流式细胞术显示,pH 7.4和pH 6.8时TAT修饰的胶束均可迅速被摄取;而pH敏感胶束在pH 7.4时进入细胞较少,pH 6.8时进入细胞增多,孵育1 h后摄取量接近TAT修饰胶束。激光共聚焦显示pH敏感胶束在pH 6.8时肿瘤细胞摄取量显著大于pH 7.4。结果说明,该胶束具有pH敏感性,pH 7.4时屏蔽TAT肽,避免其无选择性的透膜进入细胞,而在pH 6.8时暴露出TAT肽,发挥其进入细胞的能力,介导载药胶束进入肿瘤细胞,实现特异性杀伤肿瘤细胞的目的。此pH敏感胶束是一种有前景的肿瘤靶向给药系统。 Doxorubicin loaded micelles were prepared by film-hydration method using stearyl sulfadiazine (SA-SD) which is pH sensitive, methoxy (polyethylene glycol)-2000-1, 2-dioleoyl-sn-glycero-3-phosphoetha- nolamine (mPEG-DOPE) and transactivator of transcription (TAT) peptide conjugated PEG-DOPE. Mean diameter of the pH-sensitive micelles was about 20 nm with a (99.1 ±2.1) % drug entrapment efficiency at pH 7.4. Flow cytometry studies revealed that the simple TAT micelles was taken up rapidly at the same level at pH 6.8 and pH 7.4. However, the pH-sensitive micelles entered the tumor cell less at pH 7.4 and significantly increase at pH 6.8. After 1 h incubation at pH 6.8, the amount of the pH-sensitive micelles taken up by cancer cell 4T1 was almost similar to simple TAT micelles. The eonfocal microscopy indicated that the pH-sensitive micelles entered the 4T1 cells at pH 6.8 more than at pH 7.4. It was indicated that the pH-sensitive micelles could shield TAT peptide at normal pH 7.4 and deshield it at pH 6.8. Hence, TAT peptides lead the drug-loaded micelles into the tumor cells and killed them selectively. The pH-sensitive micelle may provide a novel strategy for design of cancer targeting drug delivery system.
出处 《药学学报》 CAS CSCD 北大核心 2011年第5期599-604,共6页 Acta Pharmaceutica Sinica
基金 国家自然科学基金资助项目(30873168)
关键词 细胞穿膜肽 聚合物胶束 PH敏感 阿霉素 cell-penetrating protein polymer micelle pH-sensitive doxorubicin
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