Functionalized <i>Tobacco Mosaic Virus</i> Coat Protein Monomers and Oligomers as Nanocarriers for Anti-Cancer Peptides
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 prot...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/11/10/1609 |
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| author | Coralie Gamper Caroline Spenlé Sonia Boscá Michael van der Heyden Mathieu Erhardt Gertraud Orend Dominique Bagnard Manfred Heinlein |
| author_facet | Coralie Gamper Caroline Spenlé Sonia Boscá Michael van der Heyden Mathieu Erhardt Gertraud Orend Dominique Bagnard Manfred Heinlein |
| author_sort | Coralie Gamper |
| collection | DOAJ |
| description | 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 <i>Tobacco mosaic virus</i> (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. |
| first_indexed | 2024-03-12T19:14:17Z |
| format | Article |
| id | doaj.art-a754112617a34a648983f8e30c82dd37 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T19:14:17Z |
| publishDate | 2019-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-a754112617a34a648983f8e30c82dd372023-08-02T05:36:54ZengMDPI AGCancers2072-66942019-10-011110160910.3390/cancers11101609cancers11101609Functionalized <i>Tobacco Mosaic Virus</i> Coat Protein Monomers and Oligomers as Nanocarriers for Anti-Cancer PeptidesCoralie Gamper0Caroline Spenlé1Sonia Boscá2Michael van der Heyden3Mathieu Erhardt4Gertraud Orend5Dominique Bagnard6Manfred Heinlein7Institut de Biologie Moléculaire des Plantes (IBMP-CNRS), Université de Strasbourg, 67000 Strasbourg, FranceInstitut de Biologie Moléculaire des Plantes (IBMP-CNRS), Université de Strasbourg, 67000 Strasbourg, FranceInstitut de Biologie Moléculaire des Plantes (IBMP-CNRS), Université de Strasbourg, 67000 Strasbourg, FranceINSERM 1119, BMNST Laboratory, Université de Strasbourg, 67000 Strasbourg, FranceInstitut de Biologie Moléculaire des Plantes (IBMP-CNRS), Université de Strasbourg, 67000 Strasbourg, FranceLabex Medalis, Université de Strasbourg, 67000 Strasbourg, FranceINSERM 1119, BMNST Laboratory, Université de Strasbourg, 67000 Strasbourg, FranceInstitut de Biologie Moléculaire des Plantes (IBMP-CNRS), Université de Strasbourg, 67000 Strasbourg, FranceComponents 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 <i>Tobacco mosaic virus</i> (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.https://www.mdpi.com/2072-6694/11/10/1609plant virustobacco mosaic virusnanoparticlenanocarriercancerangiogenesisneuropilin-1 |
| spellingShingle | Coralie Gamper Caroline Spenlé Sonia Boscá Michael van der Heyden Mathieu Erhardt Gertraud Orend Dominique Bagnard Manfred Heinlein Functionalized <i>Tobacco Mosaic Virus</i> Coat Protein Monomers and Oligomers as Nanocarriers for Anti-Cancer Peptides Cancers plant virus tobacco mosaic virus nanoparticle nanocarrier cancer angiogenesis neuropilin-1 |
| title | Functionalized <i>Tobacco Mosaic Virus</i> Coat Protein Monomers and Oligomers as Nanocarriers for Anti-Cancer Peptides |
| title_full | Functionalized <i>Tobacco Mosaic Virus</i> Coat Protein Monomers and Oligomers as Nanocarriers for Anti-Cancer Peptides |
| title_fullStr | Functionalized <i>Tobacco Mosaic Virus</i> Coat Protein Monomers and Oligomers as Nanocarriers for Anti-Cancer Peptides |
| title_full_unstemmed | Functionalized <i>Tobacco Mosaic Virus</i> Coat Protein Monomers and Oligomers as Nanocarriers for Anti-Cancer Peptides |
| title_short | Functionalized <i>Tobacco Mosaic Virus</i> Coat Protein Monomers and Oligomers as Nanocarriers for Anti-Cancer Peptides |
| title_sort | functionalized i tobacco mosaic virus i coat protein monomers and oligomers as nanocarriers for anti cancer peptides |
| topic | plant virus tobacco mosaic virus nanoparticle nanocarrier cancer angiogenesis neuropilin-1 |
| url | https://www.mdpi.com/2072-6694/11/10/1609 |
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