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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...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
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
Descripción
Sumario: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.