Yu Ping, Xia Xi-Ming, Wu Ming, Cui Can, Zhang Yang, Liu Lei, Wu Bo, Wang Cai-Xia, Zhang Liu-Jie, Zhou Xiang, Zhuo Ren-Xi, Huang Shi-Wen
Key Laboratory of Biomedical Polymers, Ministry of Education; Department of Chemistry, Wuhan University, Wuhan 430072, Hubei, PR China.
Key Laboratory of Biomedical Polymers, Ministry of Education; Department of Chemistry, Wuhan University, Wuhan 430072, Hubei, PR China.
Colloids Surf B Biointerfaces. 2014 Aug 1;120:142-51. doi: 10.1016/j.colsurfb.2014.05.018. Epub 2014 May 22.
Iron oxide porous nanorods (IOPNR) with lengths ranging from 40nm to 60nm and pore diameters ranging from 5nm to 10nm were prepared, and further modified with NH2-PEG-FA (FA-PEG-IOPNR) for ligand targeting and modified with NH2-PEG-OCH3 (PEG-IOPNR) as a control. Instead of chemical bonding, doxorubicin (DOX), a low water solubility anticancer drug, was loaded in the pores of the modified IOPNR because of their porous structure and high porosity. The release of DOX in acidic PBS solution (pH 5.3) was faster than that in neutral (pH 7.4) solution. The analysis results from TEM, inductively coupled plasma emission spectroscopy, confocal laser scanning microscopy, and flow cytometry analyses indicated that the presence of FA on the surface of the nanorods increase the cellular uptake of nanorods in the case of HeLa cells, a folate receptor (FR)-positive cell line. In contrast, for COS 7 cells, a FR-negative cell line, FA ligand on the surface of the nanorods showed no effect on the cellular uptake. MTT assay indicated that the cytotoxicity of DOX loaded in FA-PEG-IOPNR to HeLa cells was higher than that of DOX in PEG-IOPNR. In the case of COS 7 cells, no significant difference between the cytotoxicity of DOX loaded in FA-PEG-IOPNR and PEG-IOPNR was found. These results suggested that FA-PEG-IOPNR had the potential for target delivery of chemotherapeutic into cancer cells.
制备了长度在40纳米至60纳米之间、孔径在5纳米至10纳米之间的氧化铁多孔纳米棒（IOPNR），并用NH2-PEG-FA（FA-PEG-IOPNR）进行配体靶向修饰，并用NH2-PEG-OCH3（PEG-IOPNR）作为对照进行修饰。由于其多孔结构和高孔隙率，低水溶性抗癌药物阿霉素（DOX）被载入修饰后的IOPNR的孔中，而非通过化学键合。DOX在酸性PBS溶液（pH 5.3）中的释放速度比在中性（pH 7.4）溶液中更快。透射电子显微镜、电感耦合等离子体发射光谱、共聚焦激光扫描显微镜和流式细胞术分析的结果表明，在叶酸受体（FR）阳性细胞系HeLa细胞的情况下，纳米棒表面FA的存在增加了纳米棒的细胞摄取。相反，对于FR阴性细胞系COS 7细胞，纳米棒表面的FA配体对细胞摄取没有影响。MTT分析表明，载入FA-PEG-IOPNR中的DOX对HeLa细胞的细胞毒性高于载入PEG-IOPNR中的DOX。在COS 7细胞的情况下，未发现载入FA-PEG-IOPNR中的DOX与PEG-IOPNR中的DOX的细胞毒性之间存在显著差异。这些结果表明，FA-PEG-IOPNR具有将化疗药物靶向递送至癌细胞的潜力。
