Synthesis and biophysical evaluation of carbosilane dendrimers as therapeutic siRNA carriers
Abstract Gene therapy presents an innovative approach to the treatment of previously incurable diseases. The advancement of research in the field of nanotechnology has the potential to overcome the current limitations and challenges of conventional therapy methods, and therefore to unlocking the ful...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-51238-w |
| _version_ | 1827377363248218112 |
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| author | Serafin Zawadzki Ángela Martín-Serrano Elżbieta Okła Marta Kędzierska Sandra Garcia-Gallego Paula O. López Francisco J. de la Mata Sylwia Michlewska Tomasz Makowski Maksim Ionov Elżbieta Pędziwiatr-Werbicka Maria Bryszewska Katarzyna Miłowska |
| author_facet | Serafin Zawadzki Ángela Martín-Serrano Elżbieta Okła Marta Kędzierska Sandra Garcia-Gallego Paula O. López Francisco J. de la Mata Sylwia Michlewska Tomasz Makowski Maksim Ionov Elżbieta Pędziwiatr-Werbicka Maria Bryszewska Katarzyna Miłowska |
| author_sort | Serafin Zawadzki |
| collection | DOAJ |
| description | Abstract Gene therapy presents an innovative approach to the treatment of previously incurable diseases. The advancement of research in the field of nanotechnology has the potential to overcome the current limitations and challenges of conventional therapy methods, and therefore to unlocking the full potential of dendrimers for use in the gene therapy of neurodegenerative disorders. The blood–brain barrier (BBB) poses a significant challenge when delivering therapeutic agents to the central nervous system. In this study, we investigated the biophysical properties of dendrimers and their complexes with siRNA directed against the apolipoprotein E (APOE) gene to identify an appropriate nanocarrier capable of safely delivering the cargo across the BBB. Our study yielded valuable insights into the complexation process, stability over time, the mechanisms of interaction, the influence of dendrimers on the oligonucleotide's spatial structure, and the potential cytotoxic effects on human cerebral microvascular endothelium cells. Based on our findings, we identified that the dendrimer G3Si PEG6000 was an optimal candidate for further research, potentially serving as a nanocarrier capable of safely delivering therapeutic agents across the BBB for the treatment of neurodegenerative disorders. |
| first_indexed | 2024-03-08T12:38:03Z |
| format | Article |
| id | doaj.art-081066d037e7435d95e6d3a81dcdaea0 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-08T12:38:03Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-081066d037e7435d95e6d3a81dcdaea02024-01-21T12:16:56ZengNature PortfolioScientific Reports2045-23222024-01-0114111910.1038/s41598-024-51238-wSynthesis and biophysical evaluation of carbosilane dendrimers as therapeutic siRNA carriersSerafin Zawadzki0Ángela Martín-Serrano1Elżbieta Okła2Marta Kędzierska3Sandra Garcia-Gallego4Paula O. López5Francisco J. de la Mata6Sylwia Michlewska7Tomasz Makowski8Maksim Ionov9Elżbieta Pędziwiatr-Werbicka10Maria Bryszewska11Katarzyna Miłowska12Department of General Biophysics, Faculty of Biology and Environmental Protection, University of LodzDepartment of Organic and Inorganic Chemistry, IQAR, University of AlcaláDepartment of General Biophysics, Faculty of Biology and Environmental Protection, University of LodzDepartment of General Biophysics, Faculty of Biology and Environmental Protection, University of LodzDepartment of Organic and Inorganic Chemistry, IQAR, University of AlcaláDepartment of Organic and Inorganic Chemistry, IQAR, University of AlcaláDepartment of Organic and Inorganic Chemistry, IQAR, University of AlcaláLaboratory of Microscopic Imaging and Specialized Biological Techniques, Faculty of Biology and Environmental Protection, University of LodzCentre of Molecular and Macromolecular Studies, Polish Academy of SciencesDepartment of General Biophysics, Faculty of Biology and Environmental Protection, University of LodzDepartment of General Biophysics, Faculty of Biology and Environmental Protection, University of LodzDepartment of General Biophysics, Faculty of Biology and Environmental Protection, University of LodzDepartment of General Biophysics, Faculty of Biology and Environmental Protection, University of LodzAbstract Gene therapy presents an innovative approach to the treatment of previously incurable diseases. The advancement of research in the field of nanotechnology has the potential to overcome the current limitations and challenges of conventional therapy methods, and therefore to unlocking the full potential of dendrimers for use in the gene therapy of neurodegenerative disorders. The blood–brain barrier (BBB) poses a significant challenge when delivering therapeutic agents to the central nervous system. In this study, we investigated the biophysical properties of dendrimers and their complexes with siRNA directed against the apolipoprotein E (APOE) gene to identify an appropriate nanocarrier capable of safely delivering the cargo across the BBB. Our study yielded valuable insights into the complexation process, stability over time, the mechanisms of interaction, the influence of dendrimers on the oligonucleotide's spatial structure, and the potential cytotoxic effects on human cerebral microvascular endothelium cells. Based on our findings, we identified that the dendrimer G3Si PEG6000 was an optimal candidate for further research, potentially serving as a nanocarrier capable of safely delivering therapeutic agents across the BBB for the treatment of neurodegenerative disorders.https://doi.org/10.1038/s41598-024-51238-w |
| spellingShingle | Serafin Zawadzki Ángela Martín-Serrano Elżbieta Okła Marta Kędzierska Sandra Garcia-Gallego Paula O. López Francisco J. de la Mata Sylwia Michlewska Tomasz Makowski Maksim Ionov Elżbieta Pędziwiatr-Werbicka Maria Bryszewska Katarzyna Miłowska Synthesis and biophysical evaluation of carbosilane dendrimers as therapeutic siRNA carriers Scientific Reports |
| title | Synthesis and biophysical evaluation of carbosilane dendrimers as therapeutic siRNA carriers |
| title_full | Synthesis and biophysical evaluation of carbosilane dendrimers as therapeutic siRNA carriers |
| title_fullStr | Synthesis and biophysical evaluation of carbosilane dendrimers as therapeutic siRNA carriers |
| title_full_unstemmed | Synthesis and biophysical evaluation of carbosilane dendrimers as therapeutic siRNA carriers |
| title_short | Synthesis and biophysical evaluation of carbosilane dendrimers as therapeutic siRNA carriers |
| title_sort | synthesis and biophysical evaluation of carbosilane dendrimers as therapeutic sirna carriers |
| url | https://doi.org/10.1038/s41598-024-51238-w |
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