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近日,我院药用生物材料学科曾庆冰主任以第一及通讯作者身份Biomaterials杂志上以全文形式发表了一篇题为“Cucumber mosaic virus as drug delivery vehicle for doxorubicin”的研究论文。该研究揭示了黄瓜花叶病毒可作为抗肿瘤药物阿霉素的“智能”载体,增强其对癌细胞的杀伤力,并有效减少其心脏毒副作用。Biomaterials杂志2012年影响因子为7.404,为生物材料领域的一区杂志。该论文受到国家自然科学基金等项目的资助,我校基础医学院细胞生物教研室和南方医院心内科参与了这项研究。
Biomaterials. 2013 Jun;34(19):4632-42.
Cucumber mosaic virus as drug delivery vehicle for doxorubicin.
Zeng Q*, Wen H, Wen Q, Chen X, Wang Y, Xuan W, Liang J, Wan S.
Abstract
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-Doxnanoconjugates 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.