Functionalized Coat Protein Monomers and Oligomers as Nanocarriers for Anti-Cancer Peptides.
Fiche publication
Date publication
octobre 2019
Journal
Cancers
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BAGNARD Dominique, Dr OREND Gertraud, Dr ERHARDT Mathieu, Dr HEINLEIN Manfred
Tous les auteurs :
Gamper C, Spenlé C, Boscá S, van der Heyden M, Erhardt M, Orend G, Bagnard D, Heinlein M
Lien Pubmed
Résumé
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 (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.
Mots clés
angiogenesis, cancer, nanocarrier, nanoparticle, neuropilin-1, plant virus, tobacco mosaic virus
Référence
Cancers (Basel). 2019 Oct 22;11(10):