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LRP-1 functionalized polymersomes enhance the efficacy of carnosine in experimental stroke
Stroke is one of the commonest causes of death with limited treatment options. L-Carnosine has shown great promise as a neuroprotective agent in experimental stroke, but translation to the clinic is impeded by the large doses needed. We developed and evaluated the therapeutic potential of a novel de...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971073/ https://www.ncbi.nlm.nih.gov/pubmed/31959846 http://dx.doi.org/10.1038/s41598-020-57685-5 |
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author | Kim, Eun-Sun Kim, Donghyun Nyberg, Sophie Poma, Alessandro Cecchin, Denis Jain, Saurabh A. Kim, Kyeong-A Shin, Young-Jun Kim, Eun-Hye Kim, Minyeong Baek, Seung-Hoon Kim, Jin-Ki Doeppner, Thorsten R. Ali, Ali Redgrave, Jessica Battaglia, Giuseppe Majid, Arshad Bae, Ok-Nam |
author_facet | Kim, Eun-Sun Kim, Donghyun Nyberg, Sophie Poma, Alessandro Cecchin, Denis Jain, Saurabh A. Kim, Kyeong-A Shin, Young-Jun Kim, Eun-Hye Kim, Minyeong Baek, Seung-Hoon Kim, Jin-Ki Doeppner, Thorsten R. Ali, Ali Redgrave, Jessica Battaglia, Giuseppe Majid, Arshad Bae, Ok-Nam |
author_sort | Kim, Eun-Sun |
collection | PubMed |
description | Stroke is one of the commonest causes of death with limited treatment options. L-Carnosine has shown great promise as a neuroprotective agent in experimental stroke, but translation to the clinic is impeded by the large doses needed. We developed and evaluated the therapeutic potential of a novel delivery vehicle which encapsulated carnosine in lipoprotein receptor related protein-1 (LRP-1)-targeted functionalized polymersomes in experimental ischemic stroke. We found that following ischemic stroke, polymersomes encapsulating carnosine exhibited remarkable neuroprotective effects with a dose of carnosine 3 orders of magnitude lower than free carnosine. The LRP-1-targeted functionalization was essential for delivery of carnosine to the brain, as non-targeted carnosine polymersomes did not exhibit neuroprotection. Using Cy3 fluorescence in vivo imaging, we showed that unlike non-targeted carnosine polymersomes, LRP-1-targeted carriers accumulated in brain in a time dependent manner. Our findings suggest that these novel carriers have the ability to deliver neuroprotective cargo effectively to the brain. |
format | Online Article Text |
id | pubmed-6971073 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-69710732020-01-27 LRP-1 functionalized polymersomes enhance the efficacy of carnosine in experimental stroke Kim, Eun-Sun Kim, Donghyun Nyberg, Sophie Poma, Alessandro Cecchin, Denis Jain, Saurabh A. Kim, Kyeong-A Shin, Young-Jun Kim, Eun-Hye Kim, Minyeong Baek, Seung-Hoon Kim, Jin-Ki Doeppner, Thorsten R. Ali, Ali Redgrave, Jessica Battaglia, Giuseppe Majid, Arshad Bae, Ok-Nam Sci Rep Article Stroke is one of the commonest causes of death with limited treatment options. L-Carnosine has shown great promise as a neuroprotective agent in experimental stroke, but translation to the clinic is impeded by the large doses needed. We developed and evaluated the therapeutic potential of a novel delivery vehicle which encapsulated carnosine in lipoprotein receptor related protein-1 (LRP-1)-targeted functionalized polymersomes in experimental ischemic stroke. We found that following ischemic stroke, polymersomes encapsulating carnosine exhibited remarkable neuroprotective effects with a dose of carnosine 3 orders of magnitude lower than free carnosine. The LRP-1-targeted functionalization was essential for delivery of carnosine to the brain, as non-targeted carnosine polymersomes did not exhibit neuroprotection. Using Cy3 fluorescence in vivo imaging, we showed that unlike non-targeted carnosine polymersomes, LRP-1-targeted carriers accumulated in brain in a time dependent manner. Our findings suggest that these novel carriers have the ability to deliver neuroprotective cargo effectively to the brain. Nature Publishing Group UK 2020-01-20 /pmc/articles/PMC6971073/ /pubmed/31959846 http://dx.doi.org/10.1038/s41598-020-57685-5 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Kim, Eun-Sun Kim, Donghyun Nyberg, Sophie Poma, Alessandro Cecchin, Denis Jain, Saurabh A. Kim, Kyeong-A Shin, Young-Jun Kim, Eun-Hye Kim, Minyeong Baek, Seung-Hoon Kim, Jin-Ki Doeppner, Thorsten R. Ali, Ali Redgrave, Jessica Battaglia, Giuseppe Majid, Arshad Bae, Ok-Nam LRP-1 functionalized polymersomes enhance the efficacy of carnosine in experimental stroke |
title | LRP-1 functionalized polymersomes enhance the efficacy of carnosine in experimental stroke |
title_full | LRP-1 functionalized polymersomes enhance the efficacy of carnosine in experimental stroke |
title_fullStr | LRP-1 functionalized polymersomes enhance the efficacy of carnosine in experimental stroke |
title_full_unstemmed | LRP-1 functionalized polymersomes enhance the efficacy of carnosine in experimental stroke |
title_short | LRP-1 functionalized polymersomes enhance the efficacy of carnosine in experimental stroke |
title_sort | lrp-1 functionalized polymersomes enhance the efficacy of carnosine in experimental stroke |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971073/ https://www.ncbi.nlm.nih.gov/pubmed/31959846 http://dx.doi.org/10.1038/s41598-020-57685-5 |
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