BBB pathophysiology–independent delivery of siRNA in traumatic brain injury
Copyright © 2021 The Authors, some rights reserved. Small interfering RNA (siRNA)–based therapeutics can mitigate the long-term sequelae of traumatic brain injury (TBI) but suffer from poor permeability across the blood-brain barrier (BBB). One approach to overcoming this challenge involves treatmen...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Association for the Advancement of Science (AAAS)
2021
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| Online Access: | https://hdl.handle.net/1721.1/134128 |
| _version_ | 1826200728618663936 |
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| author | Li, Wen Qiu, Jianhua Li, Xiang-Ling Aday, Sezin Zhang, Jingdong Conley, Grace Xu, Jun Joseph, John Lan, Haoyue Langer, Robert Mannix, Rebekah Karp, Jeffrey M Joshi, Nitin |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Li, Wen Qiu, Jianhua Li, Xiang-Ling Aday, Sezin Zhang, Jingdong Conley, Grace Xu, Jun Joseph, John Lan, Haoyue Langer, Robert Mannix, Rebekah Karp, Jeffrey M Joshi, Nitin |
| author_sort | Li, Wen |
| collection | MIT |
| description | Copyright © 2021 The Authors, some rights reserved. Small interfering RNA (siRNA)–based therapeutics can mitigate the long-term sequelae of traumatic brain injury (TBI) but suffer from poor permeability across the blood-brain barrier (BBB). One approach to overcoming this challenge involves treatment administration while BBB is transiently breached after injury. However, it offers a limited window for therapeutic intervention and is applicable to only a subset of injuries with substantially breached BBB. We report a nanoparticle platform for BBB pathophysiology–independent delivery of siRNA in TBI. We achieved this by combined modulation of surface chemistry and coating density on nanoparticles, which maximized their active transport across BBB. Engineered nanoparticles injected within or outside the window of breached BBB in TBI mice showed threefold higher brain accumulation compared to nonengineered PEGylated nanoparticles and 50% gene silencing. Together, our data suggest that this nanoparticle platform is a promising next-generation drug delivery approach for the treatment of TBI. |
| first_indexed | 2024-09-23T11:40:53Z |
| format | Article |
| id | mit-1721.1/134128 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:40:53Z |
| publishDate | 2021 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/1341282024-02-05T19:25:29Z BBB pathophysiology–independent delivery of siRNA in traumatic brain injury Li, Wen Qiu, Jianhua Li, Xiang-Ling Aday, Sezin Zhang, Jingdong Conley, Grace Xu, Jun Joseph, John Lan, Haoyue Langer, Robert Mannix, Rebekah Karp, Jeffrey M Joshi, Nitin Massachusetts Institute of Technology. Department of Chemical Engineering Koch Institute for Integrative Cancer Research at MIT Harvard University--MIT Division of Health Sciences and Technology Copyright © 2021 The Authors, some rights reserved. Small interfering RNA (siRNA)–based therapeutics can mitigate the long-term sequelae of traumatic brain injury (TBI) but suffer from poor permeability across the blood-brain barrier (BBB). One approach to overcoming this challenge involves treatment administration while BBB is transiently breached after injury. However, it offers a limited window for therapeutic intervention and is applicable to only a subset of injuries with substantially breached BBB. We report a nanoparticle platform for BBB pathophysiology–independent delivery of siRNA in TBI. We achieved this by combined modulation of surface chemistry and coating density on nanoparticles, which maximized their active transport across BBB. Engineered nanoparticles injected within or outside the window of breached BBB in TBI mice showed threefold higher brain accumulation compared to nonengineered PEGylated nanoparticles and 50% gene silencing. Together, our data suggest that this nanoparticle platform is a promising next-generation drug delivery approach for the treatment of TBI. 2021-10-27T19:58:14Z 2021-10-27T19:58:14Z 2021 2021-06-17T16:03:12Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/134128 en 10.1126/sciadv.abd6889 Science Advances Creative Commons Attribution NonCommercial License 4.0 https://creativecommons.org/licenses/by-nc/4.0/ application/pdf American Association for the Advancement of Science (AAAS) Science Advances |
| spellingShingle | Li, Wen Qiu, Jianhua Li, Xiang-Ling Aday, Sezin Zhang, Jingdong Conley, Grace Xu, Jun Joseph, John Lan, Haoyue Langer, Robert Mannix, Rebekah Karp, Jeffrey M Joshi, Nitin BBB pathophysiology–independent delivery of siRNA in traumatic brain injury |
| title | BBB pathophysiology–independent delivery of siRNA in traumatic brain injury |
| title_full | BBB pathophysiology–independent delivery of siRNA in traumatic brain injury |
| title_fullStr | BBB pathophysiology–independent delivery of siRNA in traumatic brain injury |
| title_full_unstemmed | BBB pathophysiology–independent delivery of siRNA in traumatic brain injury |
| title_short | BBB pathophysiology–independent delivery of siRNA in traumatic brain injury |
| title_sort | bbb pathophysiology independent delivery of sirna in traumatic brain injury |
| url | https://hdl.handle.net/1721.1/134128 |
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