Retargeting of adenoviral gene delivery via Herceptin-PEG-adenovirus conjugates to breast cancer cells
Retargeting of adenoviral gene delivery via Herceptin-PEG-adenovirus conjugates to breast cancer cells
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DOI：
10.1016/j.jconrel.2007.08.002
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发表时间：
2007-11-06
影响因子：
10.8
通讯作者：
Haam, Seungjoo
中科院分区：
文献类型：
--
作者：
Jung, Yukyung;Park, Hyo-Jin;Haam, Seungjoo
使用人表皮生长因子受体 2 (HER2/neu) 进行靶向腺病毒基因递送是增强聚乙二醇化腺病毒 (PEG-ADV) 转导功效的有前途的策略之一。携带绿色荧光蛋白（GFP）的腺病毒的病毒衣壳与双功能聚乙二醇（PEG）缀合。然后，PEG-ADV 的表面进一步与抗 HER2/neu 单克隆抗体 (MAb)、赫赛汀 (Trastuzumab；HER) 结合，赋予 HER2/neu 过表达的乳腺癌细胞特异性靶向作用。与裸露 ADV 相比，评估了 PEG-ADV 和赫赛汀固定化 PEG-ADV (HER-PEG-ADV) 的重定向程度。总之，对于 MDA-MB-435 和 MDA-MB-468 细胞（HER2/neu 阳性细胞系），HER-PEG-ADV 表现出比 PEG-ADV 更高的 GFP 表达水平，但对于 HER2/neu 缺陷型 U251N 细胞则不然。从巨噬细胞释放的白细胞介素 6 的量判断，聚乙二醇化 ADV 同样显着降低先天免疫反应。因此，本研究表明，HER-PEG-ADV 缀合物通过克服 ADV 针对免疫系统和非特异性的局限性，使 ADV 成为更有潜力的治疗工具。 (C) 2007 Elsevier B.V. 保留所有权利。
Targeted adenoviral gene delivery using human epidermal growth factor receptor 2 (HER2/neu) is one of the promising strategies for enhancing the transduction efficacy of PEGylated adenovirus (PEG-ADV). The viral capsid of adenovirus carrying the green fluorescent protein (GFP) was conjugated with bifunctional polyethylene glycol (PEG). The surface of PEG-ADV was then further conjugated with anti-HER2/neu monoclonal antibody (MAb), Herceptin (Trastuzumab; HER) to grant HER2/neu over-expressed breast cancer cells specific targeting. The PEG-ADV and Herceptin immobilized PEG-ADV (HER-PEG-ADV) extents of retargeting were evaluated, as compared to those of naked ADV. In summary, HER-PEG-ADV exhibited more enhanced level of GFP expression than PEG-ADV did for MDA-MB-435 and MDA-MB-468 cells (a HER2/neu positive cell line), but not for a HER2/neu deficient U251N cells. PEGylated ADV significantly reduced innate immune response likewise, as judged from the amount of interleukin 6 released from macrophage cells. Consequently, this study suggests that HER-PEG-ADV conjugates enable ADV to become more potential therapeutic tools through overcoming the limitation of ADV against immune system and non-specificity. (C) 2007 Elsevier B.V. All rights reserved.