Performance of Pyridylthiourea‐Polyethylenimine Polyplex for siRNA‐Mediated Liver Cancer Therapy in Cell Monolayer, Spheroid, and Tumor Xenograft Models
Medical application of siRNAs relies on methods for delivering nucleic acids into the cytosol. Synthetic carriers, which assemble with nucleic acids into delivery systems, show promises for cancer therapy but efficiency remains to be improved. In here, the effectiveness of pyridylthiourea‐polyethyle...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2017-07-01
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| Series: | Global Challenges |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/gch2.201700013 |
| _version_ | 1797743696932765696 |
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| author | Jean Baptiste Gossart Etienne Pascal Florent Meyer Emilie Heuillard Mathieu Gonçalves Francine Gossé Eric Robinet Benoît Frisch Cendrine Seguin Guy Zuber |
| author_facet | Jean Baptiste Gossart Etienne Pascal Florent Meyer Emilie Heuillard Mathieu Gonçalves Francine Gossé Eric Robinet Benoît Frisch Cendrine Seguin Guy Zuber |
| author_sort | Jean Baptiste Gossart |
| collection | DOAJ |
| description | Medical application of siRNAs relies on methods for delivering nucleic acids into the cytosol. Synthetic carriers, which assemble with nucleic acids into delivery systems, show promises for cancer therapy but efficiency remains to be improved. In here, the effectiveness of pyridylthiourea‐polyethylenimine (πPEI), a siRNA carrier that favors both polyplex disassembly and endosome rupture upon sensing the acidic endosomal environment, in 3 experimental models of hepatocellular cancer is tested. The πPEI‐assisted delivery of a siRNA targeting the polo‐like kinase 1 into Huh‐7 monolayer produces a 90% cell death via a demonstrated RNA interference mechanism. Incubation of polyplex with Huh‐7 spheroids leads to siRNA delivery into the superficial first cell layer and a 60% reduction in spheroid growth compared to untreated controls. Administration of polyplexes into mice bearing subcutaneous implanted Huh‐7Luc tumors results in a reduced tumor progression, similar to the one observed in the spheroid model. Altogether, these results support the in vivo use of synthetic and dedicated polymers for increasing siRNA‐mediated gene knockdown, and their clinical promise in cancer therapeutics. |
| first_indexed | 2024-03-12T14:59:09Z |
| format | Article |
| id | doaj.art-0c8fe974fe604868974348546fcd08f3 |
| institution | Directory Open Access Journal |
| issn | 2056-6646 |
| language | English |
| last_indexed | 2024-03-12T14:59:09Z |
| publishDate | 2017-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Global Challenges |
| spelling | doaj.art-0c8fe974fe604868974348546fcd08f32023-08-14T09:40:43ZengWileyGlobal Challenges2056-66462017-07-0114n/an/a10.1002/gch2.201700013Performance of Pyridylthiourea‐Polyethylenimine Polyplex for siRNA‐Mediated Liver Cancer Therapy in Cell Monolayer, Spheroid, and Tumor Xenograft ModelsJean Baptiste Gossart0Etienne Pascal1Florent Meyer2Emilie Heuillard3Mathieu Gonçalves4Francine Gossé5Eric Robinet6Benoît Frisch7Cendrine Seguin8Guy Zuber9Université de Strasbourg‐CNRS CAMB UMR 7199 Faculté de Pharmacie 74 route du Rhin 67400 Illkirch FranceUniversité de Strasbourg‐CNRS CAMB UMR 7199 Faculté de Pharmacie 74 route du Rhin 67400 Illkirch FranceUniversité de Strasbourg‐INSERM UMRS 1121 Biomaterials and Bioengineering, FTMS 11 rue Humann 67000 Strasbourg FranceInstitut Hospitalo‐Universitaire de Strasbourg 1 place de l'Hôpital 67000 Strasbourg FranceInstitut Hospitalo‐Universitaire de Strasbourg 1 place de l'Hôpital 67000 Strasbourg FranceInstitut Hospitalo‐Universitaire de Strasbourg 1 place de l'Hôpital 67000 Strasbourg FranceInstitut Hospitalo‐Universitaire de Strasbourg 1 place de l'Hôpital 67000 Strasbourg FranceUniversité de Strasbourg‐CNRS CAMB UMR 7199 Faculté de Pharmacie 74 route du Rhin 67400 Illkirch FranceUniversité de Strasbourg‐CNRS CAMB UMR 7199 Faculté de Pharmacie 74 route du Rhin 67400 Illkirch FranceUniversité de Strasbourg‐CNRS, UMR 7242 Boulevard Sebastien Brant 67400 Illkirch FranceMedical application of siRNAs relies on methods for delivering nucleic acids into the cytosol. Synthetic carriers, which assemble with nucleic acids into delivery systems, show promises for cancer therapy but efficiency remains to be improved. In here, the effectiveness of pyridylthiourea‐polyethylenimine (πPEI), a siRNA carrier that favors both polyplex disassembly and endosome rupture upon sensing the acidic endosomal environment, in 3 experimental models of hepatocellular cancer is tested. The πPEI‐assisted delivery of a siRNA targeting the polo‐like kinase 1 into Huh‐7 monolayer produces a 90% cell death via a demonstrated RNA interference mechanism. Incubation of polyplex with Huh‐7 spheroids leads to siRNA delivery into the superficial first cell layer and a 60% reduction in spheroid growth compared to untreated controls. Administration of polyplexes into mice bearing subcutaneous implanted Huh‐7Luc tumors results in a reduced tumor progression, similar to the one observed in the spheroid model. Altogether, these results support the in vivo use of synthetic and dedicated polymers for increasing siRNA‐mediated gene knockdown, and their clinical promise in cancer therapeutics.https://doi.org/10.1002/gch2.201700013delivery systemliver cancerpolo‐like kinasepolyethyleniminesiRNA |
| spellingShingle | Jean Baptiste Gossart Etienne Pascal Florent Meyer Emilie Heuillard Mathieu Gonçalves Francine Gossé Eric Robinet Benoît Frisch Cendrine Seguin Guy Zuber Performance of Pyridylthiourea‐Polyethylenimine Polyplex for siRNA‐Mediated Liver Cancer Therapy in Cell Monolayer, Spheroid, and Tumor Xenograft Models Global Challenges delivery system liver cancer polo‐like kinase polyethylenimine siRNA |
| title | Performance of Pyridylthiourea‐Polyethylenimine Polyplex for siRNA‐Mediated Liver Cancer Therapy in Cell Monolayer, Spheroid, and Tumor Xenograft Models |
| title_full | Performance of Pyridylthiourea‐Polyethylenimine Polyplex for siRNA‐Mediated Liver Cancer Therapy in Cell Monolayer, Spheroid, and Tumor Xenograft Models |
| title_fullStr | Performance of Pyridylthiourea‐Polyethylenimine Polyplex for siRNA‐Mediated Liver Cancer Therapy in Cell Monolayer, Spheroid, and Tumor Xenograft Models |
| title_full_unstemmed | Performance of Pyridylthiourea‐Polyethylenimine Polyplex for siRNA‐Mediated Liver Cancer Therapy in Cell Monolayer, Spheroid, and Tumor Xenograft Models |
| title_short | Performance of Pyridylthiourea‐Polyethylenimine Polyplex for siRNA‐Mediated Liver Cancer Therapy in Cell Monolayer, Spheroid, and Tumor Xenograft Models |
| title_sort | performance of pyridylthiourea polyethylenimine polyplex for sirna mediated liver cancer therapy in cell monolayer spheroid and tumor xenograft models |
| topic | delivery system liver cancer polo‐like kinase polyethylenimine siRNA |
| url | https://doi.org/10.1002/gch2.201700013 |
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