Zhou Xu, Qin Xianyan, Gong Tao, Zhang Zhi-Rong, Fu Yao
Key Laboratory of Drug Targeting and Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
Macromol Biosci. 2017 Jul;17(7). doi: 10.1002/mabi.201600529. Epub 2017 Mar 27.
d-Fructose modified poly(ε-caprolactone)-polyethylene glycol (PCL-PEG-Fru) diblock amphiphile is synthesized via Cu(I)-catalyzed click chemistry, which self-assembles with D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) into PCL-PEG-Fru/TPGS mixed micelles (PPF MM). It has been proven that glucose transporter (GLUT)5 is overexpressed in MCF-7 cells other than L929 cells. In this study, PPF MM exhibit a significantly higher uptake efficiency than fructose-free PCL-PEG-N /TPGS mixed micelles in both 2D MCF-7 cells and 3D tumor spheroids. Also, the presence of free d-fructose competitively inhibits the internalization of PPF MM in MCF-7 cells other than L929 cells. PPF MM show selective tumor accumulation in MCF-7 breast tumor bearing mice xenografts. Taken together, PPF MM represent a promising nanoscale carrier system to achieve GLUT5-mediated cell specific delivery in cancer therapy.
通过铜（I）催化的点击化学合成了d-果糖修饰的聚（ε-己内酯）-聚乙二醇（PCL-PEG-Fru）两亲性嵌段共聚物，其与聚乙二醇1000琥珀酸酯D-α-生育酚（TPGS）自组装形成PCL-PEG-Fru/TPGS混合胶束（PPF MM）。已证实葡萄糖转运蛋白（GLUT）5在MCF-7细胞中高表达，而在L929细胞中不表达。在本研究中，PPF MM在二维MCF-7细胞和三维肿瘤球体中均表现出比不含果糖的PCL-PEG-N/TPGS混合胶束显著更高的摄取效率。此外，游离d-果糖的存在竞争性抑制了PPF MM在除L929细胞外的MCF-7细胞中的内化。PPF MM在携带MCF-7乳腺肿瘤的小鼠异种移植瘤中表现出选择性肿瘤蓄积。综上所述，PPF MM是一种有前景的纳米级载体系统，可在癌症治疗中实现GLUT5介导的细胞特异性递送。
