Saporin Toxin Delivered by Engineered Colloidal Nanoparticles Is Strongly Effective against Cancer Cells
Ribosome-inactivating proteins, including Saporin toxin, have found application in the search for innovative alternative cancer therapies to conventional chemo- and radiotherapy. Saporin’s main mechanism of action involves the inhibition of cytoplasmic protein synthesis. Its strong theoretical effic...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/7/1517 |
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| author | Lucia Salvioni Filippo Testa Linda Barbieri Marco Giustra Jessica Armida Bertolini Giulia Tomaino Paolo Tortora Davide Prosperi Miriam Colombo |
| author_facet | Lucia Salvioni Filippo Testa Linda Barbieri Marco Giustra Jessica Armida Bertolini Giulia Tomaino Paolo Tortora Davide Prosperi Miriam Colombo |
| author_sort | Lucia Salvioni |
| collection | DOAJ |
| description | Ribosome-inactivating proteins, including Saporin toxin, have found application in the search for innovative alternative cancer therapies to conventional chemo- and radiotherapy. Saporin’s main mechanism of action involves the inhibition of cytoplasmic protein synthesis. Its strong theoretical efficacy is counterbalanced by negligible cell uptake and diffusion into the cytosol. In this work, we demonstrate that by immobilizing Saporin on iron oxide nanoparticles coated with an amphiphilic polymer, which promotes nanoconjugate endosomal escape, a strong cytotoxic effect mediated by ribosomal functional inactivation can be achieved. Cancer cell death was mediated by apoptosis dependent on nanoparticle concentration but independent of surface ligand density. The cytotoxic activity of Saporin-conjugated colloidal nanoparticles proved to be selective against three different cancer cell lines in comparison with healthy fibroblasts. |
| first_indexed | 2024-03-09T10:13:34Z |
| format | Article |
| id | doaj.art-8bb24d31fd374b70b917b6245b825acc |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T10:13:34Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-8bb24d31fd374b70b917b6245b825acc2023-12-01T22:34:58ZengMDPI AGPharmaceutics1999-49232022-07-01147151710.3390/pharmaceutics14071517Saporin Toxin Delivered by Engineered Colloidal Nanoparticles Is Strongly Effective against Cancer CellsLucia Salvioni0Filippo Testa1Linda Barbieri2Marco Giustra3Jessica Armida Bertolini4Giulia Tomaino5Paolo Tortora6Davide Prosperi7Miriam Colombo8Department of Biotechnology and Bioscience, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, ItalyDepartment of Biotechnology and Bioscience, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, ItalyDepartment of Biotechnology and Bioscience, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, ItalyDepartment of Biotechnology and Bioscience, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, ItalyDepartment of Biotechnology and Bioscience, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, ItalyDepartment of Biotechnology and Bioscience, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, ItalyDepartment of Biotechnology and Bioscience, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, ItalyDepartment of Biotechnology and Bioscience, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, ItalyDepartment of Biotechnology and Bioscience, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, ItalyRibosome-inactivating proteins, including Saporin toxin, have found application in the search for innovative alternative cancer therapies to conventional chemo- and radiotherapy. Saporin’s main mechanism of action involves the inhibition of cytoplasmic protein synthesis. Its strong theoretical efficacy is counterbalanced by negligible cell uptake and diffusion into the cytosol. In this work, we demonstrate that by immobilizing Saporin on iron oxide nanoparticles coated with an amphiphilic polymer, which promotes nanoconjugate endosomal escape, a strong cytotoxic effect mediated by ribosomal functional inactivation can be achieved. Cancer cell death was mediated by apoptosis dependent on nanoparticle concentration but independent of surface ligand density. The cytotoxic activity of Saporin-conjugated colloidal nanoparticles proved to be selective against three different cancer cell lines in comparison with healthy fibroblasts.https://www.mdpi.com/1999-4923/14/7/1517ribosome-inactivating proteins (RIPs)toxinsSaporincolloidal nanoparticlescancer therapybreast cancer |
| spellingShingle | Lucia Salvioni Filippo Testa Linda Barbieri Marco Giustra Jessica Armida Bertolini Giulia Tomaino Paolo Tortora Davide Prosperi Miriam Colombo Saporin Toxin Delivered by Engineered Colloidal Nanoparticles Is Strongly Effective against Cancer Cells Pharmaceutics ribosome-inactivating proteins (RIPs) toxins Saporin colloidal nanoparticles cancer therapy breast cancer |
| title | Saporin Toxin Delivered by Engineered Colloidal Nanoparticles Is Strongly Effective against Cancer Cells |
| title_full | Saporin Toxin Delivered by Engineered Colloidal Nanoparticles Is Strongly Effective against Cancer Cells |
| title_fullStr | Saporin Toxin Delivered by Engineered Colloidal Nanoparticles Is Strongly Effective against Cancer Cells |
| title_full_unstemmed | Saporin Toxin Delivered by Engineered Colloidal Nanoparticles Is Strongly Effective against Cancer Cells |
| title_short | Saporin Toxin Delivered by Engineered Colloidal Nanoparticles Is Strongly Effective against Cancer Cells |
| title_sort | saporin toxin delivered by engineered colloidal nanoparticles is strongly effective against cancer cells |
| topic | ribosome-inactivating proteins (RIPs) toxins Saporin colloidal nanoparticles cancer therapy breast cancer |
| url | https://www.mdpi.com/1999-4923/14/7/1517 |
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