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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。
In this paper, doxorubicin-loaded polymer micelles were prepared by thin-film dispersion using pH-sensitive stearoylsmethine, mPEG2000-DOPE and transactivator of transcription peptide modified pegylated phospholipids . The pH-sensitive micelles have a particle size of about 20 nm at pH 7.4 and the entrapment efficiency of doxorubicin is (99.1 ± 2.1)%. Flow cytometry showed that the TAT-modified micelles were rapidly taken up at pH 7.4 and pH 6.8, whereas the pH-sensitive micelles entered less cells at pH 7.4 and increased into cells at pH 6.8. The uptake after 1 h incubation Close to TAT-modified micelles. Confocal laser scanning showed that the uptake of tumor cells by pH-sensitive micelles was significantly greater than pH 7.4 at pH 6.8. The results indicate that the micelles are pH-sensitive, shielding the TAT peptide at pH 7.4, preventing its non-selective permeabilization into the cell while exposing the TAT peptide at pH 6.8 to its ability to enter the cell, mediating drug loading Micelles into the tumor cells, the purpose of killing tumor cells. This pH-sensitive micelle is a promising tumor targeting drug delivery system.