Wei Yuping, Zhang Liang, Fu Yankai, Xu Xia
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, P. R. China.
J Mater Chem B. 2017 Oct 7;5(37):7768-7774. doi: 10.1039/c7tb01259d. Epub 2017 Sep 18.
Paclitaxel (PTX) is widely used to treat ovarian, breast, lung, pancreatic, cervical and other cancers, however, the cell uptake and utilization of PTX is greatly limited by its slow penetration rate and poor solubility in water. Therefore, it is of great interest to develop an efficient method for PTX delivery to improve its cellular uptake and utilization. A novel cell penetrating peptide, RRRRRWW (R7), is developed to accelerate the translocation of PTX into HeLa cells in the organic solvent-free system to suppress tumor growth. There is no significant cytotoxicity induced by the peptide alone even after 24 h incubation at 1 mM at 37 °C for both cancer cells and normal cells. In contrast, 30 min treatment with the R7/PTX complex leads to a significant decrease in the cell viability. The intracellular PTX concentration of the R7/PTX complex group is 3 fold that of the free PTX group. The in vivo animal experiments show that the tumor is dramatically suppressed by a tail vein injection of the R7/PTX complex. This system provides a novel approach for the delivery of PTX into tumor cells to efficiently suppress tumor growth.
紫杉醇（PTX）被广泛用于治疗卵巢癌、乳腺癌、肺癌、胰腺癌、宫颈癌及其他癌症，然而，PTX的细胞摄取和利用受到其缓慢的渗透速率和在水中较差的溶解度的极大限制。因此，开发一种有效的PTX递送方法以提高其细胞摄取和利用率具有重大意义。一种新型细胞穿透肽RRRRRWW（R7）被研发出来，用于在无有机溶剂体系中加速PTX转运至HeLa细胞内以抑制肿瘤生长。即使在37℃下以1 mM浓度对癌细胞和正常细胞孵育24小时后，单独的该肽也不会诱导明显的细胞毒性。相比之下，用R7/PTX复合物处理30分钟会导致细胞活力显著下降。R7/PTX复合物组的细胞内PTX浓度是游离PTX组的3倍。体内动物实验表明，通过尾静脉注射R7/PTX复合物可显著抑制肿瘤。该系统为将PTX递送至肿瘤细胞以有效抑制肿瘤生长提供了一种新方法。
