Functionalized Tobacco Mosaic Virus Coat Protein Monomers and Oligomers as Nanocarriers for Anti-Cancer Peptides

Cancers

Michael van der Heyden¹  Dominique Bagnard¹  Coralie Gamper²  Caroline Spenlé²  Sonia Boscá²  Manfred Heinlein²  Mathieu Erhardt²  Gertraud Orend³ 

[1] INSERM 1119, BMNST Laboratory, Université de Strasbourg, 67000 Strasbourg, France;Institut de Biologie Moléculaire des Plantes (IBMP-CNRS), Université de Strasbourg, 67000 Strasbourg, France;Labex Medalis, Université de Strasbourg, 67000 Strasbourg, France;

关键词: plant virus;    tobacco mosaic virus;    nanoparticle;    nanocarrier;    cancer;    angiogenesis;    neuropilin-1;   

DOI  :  10.3390/cancers11101609

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown