期刊
CANCERS
卷 11, 期 10, 页码 -出版社
MDPI
DOI: 10.3390/cancers11101609
关键词
plant virus; tobacco mosaic virus; nanoparticle; nanocarrier; cancer; angiogenesis; neuropilin-1
类别
资金
- University of Strasbourg Institute of Advanced Study (USIAS fellowship 2012)
- Ligue Contre Le Cancer (Conference de Coordination Interregionale Grand-Est, 2016)
- Ligue Contre Le Cancer (Conference de Coordination Interregionale Grand-Est, 2017)
- Ligue Nationale Contre le Cancer
- Worldwide Cancer Research [14-1070]
Components with self-assembly properties derived from plant viruses provide the opportunity to design biological nanoscaffolds for the ordered display of agents of diverse nature and with complementing functions. With the aim of designing a functionalized nanoscaffold to target cancer, the coat protein (CP) of Tobacco mosaic virus (TMV) was tested as nanocarrier for an insoluble, highly hydrophobic peptide that targets the transmembrane domain of the Neuropilin-1 (NRP1) receptor in cancer cells. The resulting construct CPL-K (CP-linker-Kill) binds to NRP1 in cancer cells and disrupts NRP1 complex formation with PlexA1 as well as downstream Akt survival signaling. The application of CPL-K also inhibits angiogenesis and cell migration. CP was also fused to a peptide that targets the extracellular domain of NRP1 and this fusion protein (CPL-F, CP-Linker-Find) is shown to bind to cultured cancer cells and to inhibit NRP1-dependent angiogenesis as well. CPL-K and CPL-F maintain their anti-angiogenic properties upon co-assembly to oligomers/nanoparticles together with CPL. The observations show that the CP of TMV can be employed to generate a functionalized nanoparticle with biological activity. Remarkably, fusion to CPL allowed us to solubilize the highly insoluble transmembrane NRP1 peptide and to retain its anti-angiogenic effect.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据