Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong.
Toxicol Appl Pharmacol. 2011 Jan 15;250(2):184-93. doi: 10.1016/j.taap.2010.10.012. Epub 2010 Oct 21.
The acquisition of multidrug resistance poses a serious problem in chemotherapy, and new types of transporters have been actively sought to overcome it. In the present study, poly(ethylene glycol)-conjugated (PEGylated) multi-walled carbon nanotubes (MWCNTs) were prepared and explored as drug carrier to overcome multidrug resistance. The prepared PEGylated MWCNTs penetrated into mammalian cells without damage plasma membrane, and its accumulation did not affect cell proliferation and cell cycle distribution. More importantly, PEGylated MWCNTs accumulated in the multidrug-resistant cancer cells as efficient as in the sensitive cancer cells. Intracellular translocation of PEGylated MWCNTs was visualized in both multidrug-resistant HepG2-DR cells and sensitive HepG2 cells, as judged by both fluorescent and transmission electron microscopy. PEGylated MWCNTs targeted cancer cells efficiently and multidrug-resistant cells failed to remove the intracellular MWCNTs. However, if used in combination with drugs without conjugation, PEGylated MWCNTs prompted drug efflux in MDR cells by stimulating the ATPase activity of P-glycoprotein. This study suggests that PEGylated MWCNTs can be developed as an efficient drug carrier to conjugate drugs for overcoming multidrug resistance in cancer chemotherapy.
多药耐药性的获得是化疗中的一个严重问题，因此人们积极寻求新的转运体来克服它。在本研究中，制备了聚乙二醇（PEG）化多壁碳纳米管（MWCNTs）并将其作为药物载体来克服多药耐药性。所制备的 PEG 化 MWCNTs 穿透哺乳动物细胞而不损伤质膜，其积累不影响细胞增殖和细胞周期分布。更重要的是，PEG 化 MWCNTs 在多药耐药性癌细胞中的积累与在敏感癌细胞中的积累一样有效。通过荧光和透射电子显微镜观察到，PEG 化 MWCNTs 能够在多药耐药性 HepG2-DR 细胞和敏感 HepG2 细胞中发生细胞内易位。PEG 化 MWCNTs 能够有效地靶向癌细胞和多药耐药性细胞，而多药耐药性细胞无法去除细胞内的 MWCNTs。然而，如果与未缀合的药物联合使用，PEG 化 MWCNTs 通过刺激 P-糖蛋白的 ATP 酶活性促使 MDR 细胞中的药物外排。本研究表明，PEG 化 MWCNTs 可被开发为有效的药物载体，与药物缀合以克服癌症化疗中的多药耐药性。
