Destito Giuseppe, Yeh Robert, Rae Chris S, Finn M G, Manchester Marianne
Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla CA 92037, USA.
Chem Biol. 2007 Oct;14(10):1152-62. doi: 10.1016/j.chembiol.2007.08.015.
Cowpea mosaic virus (CPMV) is a well-characterized nanoparticle that has been used for a variety of nanobiotechnology applications. CPMV interacts with several mammalian cell lines and tissues in vivo. To overcome natural CPMV targeting and redirect CPMV particles to cells of interest, we attached a folic acid-PEG conjugate by using the copper-catalyzed azide-alkyne cycloaddition reaction. PEGylation of CPMV completely eliminated background binding of the virus to tumor cells. The PEG-folate moiety allowed CPMV-specific recognition of tumor cells bearing the folate receptor. In addition, by testing CPMV formulations with different amounts of the PEG-FA moiety displayed on the surface, we show that higher-density loading of targeting ligands on CPMV may not be necessary for efficient targeting to tumor cells. These studies help to define the requirements for efficiently targeting nanoparticles and protein cages to tumors.
豇豆花叶病毒（CPMV）是一种特性明确的纳米颗粒，已被用于多种纳米生物技术应用。CPMV在体内与多种哺乳动物细胞系和组织相互作用。为了克服CPMV的天然靶向性并将CPMV颗粒重新导向目标细胞，我们通过铜催化的叠氮化物-炔烃环加成反应连接了叶酸-聚乙二醇共轭物。CPMV的聚乙二醇化完全消除了病毒与肿瘤细胞的背景结合。聚乙二醇-叶酸部分使CPMV能够特异性识别携带叶酸受体的肿瘤细胞。此外，通过测试表面展示不同量聚乙二醇-叶酸部分的CPMV制剂，我们表明在CPMV上进行更高密度的靶向配体负载对于有效靶向肿瘤细胞可能不是必需的。这些研究有助于确定将纳米颗粒和蛋白质笼有效靶向肿瘤的要求。
