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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| Veröffentlicht in: | Scientific reports 2020-01, Vol.10 (1), p.699, Article 699 |
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| creator | 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 |
| 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. |
| doi_str_mv | 10.1038/s41598-020-57685-5 |
| format | Article |
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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.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-57685-5</identifier><identifier>PMID: 31959846</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>14/28 ; 631/378/340 ; 64/60 ; 692/617/375/534 ; Animals ; Brain Chemistry ; Brain damage ; Brain Ischemia - drug therapy ; Carnosine ; Carnosine - administration & dosage ; Carnosine - chemistry ; Carnosine - pharmacokinetics ; Disease Models, Animal ; Drug Carriers - chemistry ; Drug Compounding ; Drug dosages ; Humanities and Social Sciences ; Hydration ; Ischemia ; Low Density Lipoprotein Receptor-Related Protein-1 - metabolism ; Male ; Mice ; Morphology ; multidisciplinary ; Neuroimaging ; Neuroprotection ; Peptides - chemistry ; Peptides - metabolism ; Pharmaceutical sciences ; Pharmacy ; Rats ; Science ; Science (multidisciplinary) ; Stroke ; Stroke - drug therapy ; Time Factors ; Transmission electron microscopy ; Treatment Outcome</subject><ispartof>Scientific reports, 2020-01, Vol.10 (1), p.699, Article 699</ispartof><rights>The Author(s) 2020</rights><rights>This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-51c16a3ab9320c16a87f3c8afcded7584275201a15a0f215ba62c135b7b375723</citedby><cites>FETCH-LOGICAL-c474t-51c16a3ab9320c16a87f3c8afcded7584275201a15a0f215ba62c135b7b375723</cites><orcidid>0000-0003-2913-0389</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971073/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971073/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31959846$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Eun-Sun</creatorcontrib><creatorcontrib>Kim, Donghyun</creatorcontrib><creatorcontrib>Nyberg, Sophie</creatorcontrib><creatorcontrib>Poma, Alessandro</creatorcontrib><creatorcontrib>Cecchin, Denis</creatorcontrib><creatorcontrib>Jain, Saurabh A.</creatorcontrib><creatorcontrib>Kim, Kyeong-A</creatorcontrib><creatorcontrib>Shin, Young-Jun</creatorcontrib><creatorcontrib>Kim, Eun-Hye</creatorcontrib><creatorcontrib>Kim, Minyeong</creatorcontrib><creatorcontrib>Baek, Seung-Hoon</creatorcontrib><creatorcontrib>Kim, Jin-Ki</creatorcontrib><creatorcontrib>Doeppner, Thorsten R.</creatorcontrib><creatorcontrib>Ali, Ali</creatorcontrib><creatorcontrib>Redgrave, Jessica</creatorcontrib><creatorcontrib>Battaglia, Giuseppe</creatorcontrib><creatorcontrib>Majid, Arshad</creatorcontrib><creatorcontrib>Bae, Ok-Nam</creatorcontrib><title>LRP-1 functionalized polymersomes enhance the efficacy of carnosine in experimental stroke</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><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.</description><subject>14/28</subject><subject>631/378/340</subject><subject>64/60</subject><subject>692/617/375/534</subject><subject>Animals</subject><subject>Brain Chemistry</subject><subject>Brain damage</subject><subject>Brain Ischemia - drug therapy</subject><subject>Carnosine</subject><subject>Carnosine - administration & dosage</subject><subject>Carnosine - chemistry</subject><subject>Carnosine - pharmacokinetics</subject><subject>Disease Models, Animal</subject><subject>Drug Carriers - chemistry</subject><subject>Drug Compounding</subject><subject>Drug dosages</subject><subject>Humanities and Social Sciences</subject><subject>Hydration</subject><subject>Ischemia</subject><subject>Low Density Lipoprotein Receptor-Related Protein-1 - metabolism</subject><subject>Male</subject><subject>Mice</subject><subject>Morphology</subject><subject>multidisciplinary</subject><subject>Neuroimaging</subject><subject>Neuroprotection</subject><subject>Peptides - chemistry</subject><subject>Peptides - metabolism</subject><subject>Pharmaceutical sciences</subject><subject>Pharmacy</subject><subject>Rats</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Stroke</subject><subject>Stroke - drug therapy</subject><subject>Time Factors</subject><subject>Transmission electron microscopy</subject><subject>Treatment Outcome</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kU1rFTEUhoMottT-ARcl0I2bafM5yWwKUvwoXKiIbtyETO5Jb9qZ5JrMiNdfb65Ta3VhNjlwnvOeN3kReknJGSVcnxdBZacbwkgjVatlI5-gQ0aEbBhn7Omj-gAdl3JL6pGsE7R7jg447eqwaA_Rl9XHDw3Ffo5uCinaIfyANd6mYTdCLmmEgiFubHSApw1g8D4463Y4eexsjqmECDhEDN-3kMMIcbIDLlNOd_ACPfN2KHB8fx-hz2_ffLp836yu311dvl41TigxNZI62lpu-44zsi-18txp690a1kpqwZRkhFoqLfGMyt62zFEue9VzJRXjR-hi0d3O_QhrVz1kO5httWPzziQbzN-dGDbmJn0zbacoUbwKvLoXyOnrDGUyYygOhsFGSHMxjAtOBBVUV_T0H_Q2zbl-20IxpTu9d8QWyuVUSgb_YIYSs0_PLOmZmp75lZ6Rdejk8TMeRn5nVQG-AKW24g3kP7v_I_sTHWKl5g</recordid><startdate>20200120</startdate><enddate>20200120</enddate><creator>Kim, Eun-Sun</creator><creator>Kim, Donghyun</creator><creator>Nyberg, Sophie</creator><creator>Poma, Alessandro</creator><creator>Cecchin, Denis</creator><creator>Jain, Saurabh A.</creator><creator>Kim, Kyeong-A</creator><creator>Shin, Young-Jun</creator><creator>Kim, Eun-Hye</creator><creator>Kim, Minyeong</creator><creator>Baek, Seung-Hoon</creator><creator>Kim, Jin-Ki</creator><creator>Doeppner, Thorsten R.</creator><creator>Ali, Ali</creator><creator>Redgrave, Jessica</creator><creator>Battaglia, Giuseppe</creator><creator>Majid, Arshad</creator><creator>Bae, Ok-Nam</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-2913-0389</orcidid></search><sort><creationdate>20200120</creationdate><title>LRP-1 functionalized polymersomes enhance the efficacy of carnosine in experimental stroke</title><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></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-51c16a3ab9320c16a87f3c8afcded7584275201a15a0f215ba62c135b7b375723</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>14/28</topic><topic>631/378/340</topic><topic>64/60</topic><topic>692/617/375/534</topic><topic>Animals</topic><topic>Brain Chemistry</topic><topic>Brain damage</topic><topic>Brain Ischemia - drug therapy</topic><topic>Carnosine</topic><topic>Carnosine - administration & dosage</topic><topic>Carnosine - chemistry</topic><topic>Carnosine - pharmacokinetics</topic><topic>Disease Models, Animal</topic><topic>Drug Carriers - chemistry</topic><topic>Drug Compounding</topic><topic>Drug dosages</topic><topic>Humanities and Social Sciences</topic><topic>Hydration</topic><topic>Ischemia</topic><topic>Low Density Lipoprotein Receptor-Related Protein-1 - metabolism</topic><topic>Male</topic><topic>Mice</topic><topic>Morphology</topic><topic>multidisciplinary</topic><topic>Neuroimaging</topic><topic>Neuroprotection</topic><topic>Peptides - chemistry</topic><topic>Peptides - metabolism</topic><topic>Pharmaceutical sciences</topic><topic>Pharmacy</topic><topic>Rats</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Stroke</topic><topic>Stroke - drug therapy</topic><topic>Time Factors</topic><topic>Transmission electron microscopy</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Eun-Sun</creatorcontrib><creatorcontrib>Kim, Donghyun</creatorcontrib><creatorcontrib>Nyberg, Sophie</creatorcontrib><creatorcontrib>Poma, Alessandro</creatorcontrib><creatorcontrib>Cecchin, Denis</creatorcontrib><creatorcontrib>Jain, Saurabh A.</creatorcontrib><creatorcontrib>Kim, Kyeong-A</creatorcontrib><creatorcontrib>Shin, Young-Jun</creatorcontrib><creatorcontrib>Kim, Eun-Hye</creatorcontrib><creatorcontrib>Kim, Minyeong</creatorcontrib><creatorcontrib>Baek, Seung-Hoon</creatorcontrib><creatorcontrib>Kim, Jin-Ki</creatorcontrib><creatorcontrib>Doeppner, Thorsten R.</creatorcontrib><creatorcontrib>Ali, Ali</creatorcontrib><creatorcontrib>Redgrave, Jessica</creatorcontrib><creatorcontrib>Battaglia, Giuseppe</creatorcontrib><creatorcontrib>Majid, Arshad</creatorcontrib><creatorcontrib>Bae, Ok-Nam</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Eun-Sun</au><au>Kim, Donghyun</au><au>Nyberg, Sophie</au><au>Poma, Alessandro</au><au>Cecchin, Denis</au><au>Jain, Saurabh A.</au><au>Kim, Kyeong-A</au><au>Shin, Young-Jun</au><au>Kim, Eun-Hye</au><au>Kim, Minyeong</au><au>Baek, Seung-Hoon</au><au>Kim, Jin-Ki</au><au>Doeppner, Thorsten R.</au><au>Ali, Ali</au><au>Redgrave, Jessica</au><au>Battaglia, Giuseppe</au><au>Majid, Arshad</au><au>Bae, Ok-Nam</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>LRP-1 functionalized polymersomes enhance the efficacy of carnosine in experimental stroke</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-01-20</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>699</spage><pages>699-</pages><artnum>699</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31959846</pmid><doi>10.1038/s41598-020-57685-5</doi><orcidid>https://orcid.org/0000-0003-2913-0389</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Nature Free; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry; Springer Nature OA Free Journals |
| subjects | 14/28 631/378/340 64/60 692/617/375/534 Animals Brain Chemistry Brain damage Brain Ischemia - drug therapy Carnosine Carnosine - administration & dosage Carnosine - chemistry Carnosine - pharmacokinetics Disease Models, Animal Drug Carriers - chemistry Drug Compounding Drug dosages Humanities and Social Sciences Hydration Ischemia Low Density Lipoprotein Receptor-Related Protein-1 - metabolism Male Mice Morphology multidisciplinary Neuroimaging Neuroprotection Peptides - chemistry Peptides - metabolism Pharmaceutical sciences Pharmacy Rats Science Science (multidisciplinary) Stroke Stroke - drug therapy Time Factors Transmission electron microscopy Treatment Outcome |
| title | LRP-1 functionalized polymersomes enhance the efficacy of carnosine in experimental stroke |
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