Biotinylated Bionanocapsules for Displaying Diverse Ligands Toward Cell-specific Delivery

Biotinylated Bionanocapsules for Displaying Diverse Ligands Toward Cell-specific Delivery
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DOI:
10.1093/jb/mvp134
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发表时间:
2009-12-01
影响因子:
2.7
通讯作者:
Kondo, Akihiko
Kondo, Akihiko
中科院分区:
生物学4区
文献类型:
--
作者:
Shishido, Takuya;Azumi, Yuki;Kondo, Akihiko

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生物纳米胶囊(BNC)是由乙型肝炎病毒表面抗原的l蛋白组成的中空纳米颗粒。BNC允许将基因或药物靶向递送到肝细胞,而不是其他类型的细胞。在这项研究中,我们试图通过插入生物素受体肽(BAP)来改变BNC的特异性,BAP可以利用大肠杆菌中的生物素连接酶BirA有效地进行生物素化。利用链亲和素作为连接体,生物素化的BNC可以显示各种难以与BNC融合的生物素化配体,如抗体、合成肽和功能分子。BNC被有效地生物素化并有效地显示链霉亲和素。此外,我们证明了生物素化的BNC通过生物素化的纳米体显示在BNC表面被内化到靶细胞中。生物素化的BNC允许展示不同的配体,因此有潜力作为药物递送到各种靶细胞的多功能载体。
Bionanocapsule (BNC) is hollow nanoparticle composed of the l-protein of the hepatitis B virus surface antigen. BNC allows targeted delivery of either genes or drugs only to hepatocytes, but not to other cell types. In this study, we attempted to alter the specificity of BNC by insertion of biotin-acceptor peptide (BAP), which is efficiently biotinylated using biotin ligase BirA from Escherichia coli. Using streptavidin as a linker, biotinylated BNC could be display various biotinylated ligands that are otherwise difficult to fuse with BNC, such as antibodies, synthetic peptides and functional molecules. BAP-fused BNC was efficiently biotinylated and effectively displayed streptavidin. Furthermore, we demonstrated that biotinylated BNC was internalized into targeted cells via biotinylated Nanobody displayed on the BNC surface. Biotinylated BNC permit display of diverse ligands, and thus have potential as a versatile carrier for drug delivery to a variety of target cells.