Cucumber mosaic virus as drug delivery vehicle for doxorubicin.
Cucumber mosaic virus as drug delivery vehicle for doxorubicin.
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DOI：
10.1016/j.biomaterials.2013.03.017
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发表时间：
2013-06
期刊：
影响因子：
14
通讯作者：
Qingbing Zeng;Hanbin Wen;Qing Wen;Xiaohui Chen;Yuegang Wang;Wanling Xuan;Jiansheng Liang;Shanhe Wan
中科院分区：
文献类型：
--
作者：
Qingbing Zeng;Hanbin Wen;Qing Wen;Xiaohui Chen;Yuegang Wang;Wanling Xuan;Jiansheng Liang;Shanhe Wan
利用黄瓜花叶病毒（CMV）独特的结构特点，我们将叶酸（FA）作为靶向分子锚定在CMV刚性衣壳上，并通过Dox-RNA偶联物将大量阿霉素（Dox）负载到CMV的内腔中，以提供一种用于癌症治疗的纳米控制递送系统。FA-CMV-Dox组件的特征在于使用透射电子显微镜和尺寸排阻色谱法，其公开了它们具有与天然CMV颗粒相当的尺寸和形态。负载Dox的病毒颗粒在生理pH下表现出超过5天的持续体外Dox释放曲线，但可以在存在升高水平的RNA酶的情况下从缀合物中释放。分别在小鼠心肌细胞和FR过表达OVCAR-3肿瘤细胞中，通过活细胞成像、MTT和TUNEL测定来评估叶酸受体（FR）靶向CMV-Dox纳米缀合物对细胞内化和细胞增殖的体外作用。还通过组织学改变和TUNEL评估在OVCAR-3 BALB/c裸鼠异种移植模型中研究了体内疗效。FA-CMV-Dox颗粒显著降低了Dox在小鼠心肌细胞核中的积聚，并提高了卵巢癌对Dox的摄取，从而降低了心脏毒性并增强了抗肿瘤作用。我们相信，CMV提供了一种新的方法来制造纳米药物载体。
Taking advantage of the unique structure feature of cucumber mosaic virus (CMV), we have anchored folic acid (FA) as targeting moiety on the rigid CMV capsid and loaded significant amount of doxorubicin (Dox) into the interior cavity of CMV through the formation of Dox–RNA conjugate to provide a nanosized control delivery system for cancer therapy. The FA–CMV–Dox assemblies were characterized using transmission electron microscopy and size exclusion chromatography, which disclose that they have comparable size and morphology to the native CMV particles. The Dox-loaded viral particles exhibit sustained in vitro Dox release profile over 5 days at physiological pH but can be liberated from the conjugates with the presence of elevated level of RNase. The in vitro effects of folate receptor (FR)-targeted CMV–Dox nanoconjugates on cellular internalization and cell proliferation were evaluated by live-cell imaging, MTT and TUNEL assay, respectively, in mouse cardiomyocytes and FR over expression OVCAR-3 tumor cells. The in vivo efficacy was also investigated in the OVCAR-3 BALB/c nude mouse xenograft model through histological alterations and TUNEL assessment. The FA–CMV–Dox particles significantly decrease the accumulation of Dox in the nuclei of mouse myocardial cells and improve the uptake of Dox in the ovarian cancer, leading to less cardiotoxicity and enhanced antitumor effect. We believe that CMV offers a new way to fabricate nanosized drug delivery vehicles.