Tian Ye, Gao Sijia, Wu Man, Liu Xiangxiang, Qiao Jing, Zhou Quan, Jiang Shidong, Niu Zhongwei
Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences , Beijing 100190, China.
ACS Appl Mater Interfaces. 2016 May 4;8(17):10800-7. doi: 10.1021/acsami.6b02801. Epub 2016 Apr 19.
For cancer therapy, viruses have been utilized as excellent delivery vehicles because of their facile transfection efficiency in their host cells. However, their inherent immunogenicity has become the major obstacle for their translation into approved pharmaceuticals. Herein, we utilized rodlike plant virus, tobacco mosaic virus (TMV), which is nontoxic to mammals and mainly infects tobacco species, as anticancer nanorod-drug vector for cancer therapy study. Doxorubicin (DOX) was installed in the inner cavity of TMV by hydrazone bond, which enabled the pH-sensitive drug release property. Conjugation of cyclic Arg-Gly-Asp (cRGD) on the surface of TMV can enhance HeLa cell uptake of the carrier via the integrin-mediated endocytosis pathway. Comparing with free DOX, the cRGD-TMV-hydra-DOX vector had similar cell growth inhibition and much higher apoptosis efficiency on HeLa cells. Moreover, the in vivo assay assumed that cRGD-TMV-hydra-DOX behaved similar antitumor efficiency but much lower side effect on HeLa bearing Balb/c-nu mice. Our work provides novel insights into potentially cancer therapy based on rodlike plant viral nanocarriers.
在癌症治疗中，病毒因其在宿主细胞中易于转染的效率而被用作优良的递送载体。然而，其固有的免疫原性已成为它们转化为获批药物的主要障碍。在此，我们利用对哺乳动物无毒且主要感染烟草物种的杆状植物病毒——烟草花叶病毒（TMV）作为用于癌症治疗研究的抗癌纳米棒药物载体。阿霉素（DOX）通过腙键安装在TMV的内腔中，这赋予了其pH敏感的药物释放特性。在TMV表面偶联环状精氨酸 - 甘氨酸 - 天冬氨酸（cRGD）可通过整合素介导的内吞途径增强载体对HeLa细胞的摄取。与游离DOX相比，cRGD - TMV - hydra - DOX载体对HeLa细胞具有相似的细胞生长抑制作用且凋亡效率更高。此外，体内实验表明，cRGD - TMV - hydra - DOX对荷HeLa细胞的Balb/c - nu小鼠具有相似的抗肿瘤效率但副作用小得多。我们的工作为基于杆状植物病毒纳米载体的潜在癌症治疗提供了新的见解。
