M13 Bacteriophage-Polymer Nanoassemblies as Drug Delivery Vehicles

M13 Bacteriophage-Polymer Nanoassemblies as Drug Delivery Vehicles
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DOI:
10.1007/s12274-011-0104-2
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发表时间:
2011-05-01
期刊:
影响因子:
9.9
通讯作者:
Wang, Qian
Wang, Qian
中科院分区:
材料科学1区
文献类型:
--
作者:
Suthiwangcharoen, Nisaraporn;Li, Tao;Wang, Qian

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用叶酸偶联的M13(FA-M13)包被的聚(己内酯-b-2-乙烯基吡啶)(PCL-P2 VP)提供了能够包封疏水性抗肿瘤药物如阿霉素(DOX)的纳米级递送系统。DOX负载的FA-M13-PCL-P2 VP组件具有约200 nm的平均直径,并且使用透射电子显微镜、扫描电子显微镜和动态光散射表征它们的结构。在酸性条件下DOX从纳米组装体的释放显示出比在生理pH下观察到的明显更快。此外,DOX负载的FA-M13-PCL-P2 VP颗粒显示出比叶酸受体阴性细胞明显更大的细胞摄取和对叶酸受体阳性癌细胞的细胞毒性,表明该受体通过受体介导的内吞作用促进叶酸摄取。此外,与游离DOX相比,负载DOX的颗粒还具有显著更高的肿瘤摄取和选择性。因此,本研究提供了一种新的方法来制造纳米药物载体。
Poly(caprolactone-b-2-vinylpyridine) (PCL-P2VP) coated with folate-conjugated M13 (FA-M13) provides a nanosized delivery system which is capable of encapsulating hydrophobic antitumor drugs such as doxorubicin (DOX). The DOX-loaded FA-M13-PCL-P2VP assemblies had an average diameter of approximately 200 nm and their structure was characterized using transmission electron microscopy, scanning electron microscopy, and dynamic light scattering. The particles were stable at physiological pH but could be degraded at a lower pH. The release of DOX from the nanoassemblies under acidic conditions was shown to be significantly faster than that observed at physiological pH. In addition, the DOX-loaded FA-M13-PCL-P2VP particles showed a distinctly greater cellular uptake and cytotoxicity against folate-receptor-positive cancer cells than folate-receptor-negative cells, indicating that the receptor facilitates folate uptake via receptor-mediated endocytosis. Furthermore, the DOX-loaded particles also had a significantly higher tumor uptake and selectivity compared to free DOX. This study therefore offers a new way to fabricate nanosized drug delivery vehicles.