Selection of pancreatic cancer cell-binding landscape phages and their use in development of anticancer nanomedicines
Selection of pancreatic cancer cell-binding landscape phages and their use in development of anticancer nanomedicines
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DOI：
10.1093/protein/gzu020
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发表时间：
2014-07-01
影响因子：
2.4
通讯作者：
Petrenko, Valery A.
中科院分区：
文献类型：
--
作者：
Bedi, Deepa;Gillespie, James W.;Petrenko, Valery A.
据推测，靶向药物递送系统的使用可以通过增强药物在疾病部位的积累来显著改善小分子化疗的治疗指数。噬菌体展示技术为靶向配体的筛选提供了一种高通量的方法。我们已经成功地分离出对PANC-1胰腺癌细胞具有选择性和特异性的噬菌体融合蛋白。阿霉素脂质体（Lipodox）修饰与肿瘤特异性噬菌体融合蛋白增强阿霉素的摄取，特别是在PANC-1细胞相比，未经修饰的Lipodox，也与正常乳腺上皮细胞。尽管P-糖蛋白介导的药物外排，但噬菌体蛋白靶向Lipodox显著增加了PANC-1细胞核中阿霉素的浓度。用胰腺细胞靶向Lipodox获得的体外细胞毒性活性大于未修饰的Lipodox。我们提出了一种新的和简单的方法，用于制备胰腺肿瘤靶向纳米药物锚定胰腺癌特异性噬菌体蛋白内的脂质体双层。
It is hypothesized that the use of targeted drug delivery systems can significantly improve the therapeutic index of small molecule chemotherapies by enhancing accumulation of the drugs at the site of disease. Phage display offers a high-throughput approach for selection of the targeting ligands. We have successfully isolated phage fusion proteins selective and specific for PANC-1 pancreatic cancer cells. Doxorubicin liposomes (Lipodox) modified with tumor-specific phage fusion proteins enhanced doxorubicin uptake specifically in PANC-1 cells as compared with unmodified Lipodox and also compared with normal breast epithelial cells. Phage protein-targeted Lipodox substantially increased the concentration of doxorubicin in the nuclei of PANC-1 cells in spite of P-glycoprotein-mediated drug efflux. The in vitro cytotoxic activity obtained with pancreatic cell-targeted Lipodox was greater than that of unmodified Lipodox. We present a novel and straightforward method for preparing pancreatic tumor-targeted nanomedicines by anchoring pancreatic cancer-specific phage proteins within the liposome bilayer.