Engineered exosomes mediated targeted delivery of neuroprotective peptide NR2B9c for the treatment of traumatic brain injury
Neuroprotection is one of the core treatment strategies for brain injuries including traumatic brain injury (TBI). NR2B9c is a promising neuroprotective peptide but its clinical translation is limited because of poor brain penetrability. Exosomes are naturally occurring nanovesicles having therapeut...
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Veröffentlicht in: | International journal of pharmaceutics 2024-01, Vol.649, p.123656-123656, Article 123656 |
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container_title | International journal of pharmaceutics |
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creator | Haroon, Khan Zheng, Haoran Wu, Shengju Liu, Ze Tang, Yaohui Yang, Guo-Yuan Liu, Yingli Zhang, Zhijun |
description | Neuroprotection is one of the core treatment strategies for brain injuries including traumatic brain injury (TBI). NR2B9c is a promising neuroprotective peptide but its clinical translation is limited because of poor brain penetrability. Exosomes are naturally occurring nanovesicles having therapeutic potential for TBI as well as an efficient drug delivery carrier to the brain. Here, we engineered exosomes with neuron targeting peptide rabies virus glycoprotein (RVG29) via bio-orthogonal click chemistry technique and loaded it with NR2B9c, developing RVG-Exo
. RVG29 conjugated exosome had higher neuron targeting efficiency compared to naïve exosomes both in vivo and in vitro. RVG-Exo
had great cytoprotective effect against oxygen glucose deprived Neuro2a cells. Intravenous administration of RVG-Exo
significantly improved behavioral outcomes and reduced the lesion volume after TBI injury in a mice controlled cortical impact model. Due to their multifunctionality and significant efficacy, we anticipate that RVG-Exo
have the potential to be translated both as therapeutic agent as well as cargo delivery system to the brain for the treatment of TBI. |
doi_str_mv | 10.1016/j.ijpharm.2023.123656 |
format | Article |
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. RVG29 conjugated exosome had higher neuron targeting efficiency compared to naïve exosomes both in vivo and in vitro. RVG-Exo
had great cytoprotective effect against oxygen glucose deprived Neuro2a cells. Intravenous administration of RVG-Exo
significantly improved behavioral outcomes and reduced the lesion volume after TBI injury in a mice controlled cortical impact model. Due to their multifunctionality and significant efficacy, we anticipate that RVG-Exo
have the potential to be translated both as therapeutic agent as well as cargo delivery system to the brain for the treatment of TBI.</description><identifier>ISSN: 0378-5173</identifier><identifier>EISSN: 1873-3476</identifier><identifier>DOI: 10.1016/j.ijpharm.2023.123656</identifier><identifier>PMID: 38040392</identifier><language>eng</language><publisher>Netherlands</publisher><subject>Animals ; Brain ; Brain Injuries, Traumatic - drug therapy ; Brain Injuries, Traumatic - pathology ; Drug Carriers - pharmacology ; Exosomes ; Mice ; Neuroprotection ; Peptides</subject><ispartof>International journal of pharmaceutics, 2024-01, Vol.649, p.123656-123656, Article 123656</ispartof><rights>Copyright © 2023 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c309t-bbcb77b1d1c78cd07178a77e99954ed4b58c9f3ad975b8105474be48ab351b0f3</citedby><cites>FETCH-LOGICAL-c309t-bbcb77b1d1c78cd07178a77e99954ed4b58c9f3ad975b8105474be48ab351b0f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38040392$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Haroon, Khan</creatorcontrib><creatorcontrib>Zheng, Haoran</creatorcontrib><creatorcontrib>Wu, Shengju</creatorcontrib><creatorcontrib>Liu, Ze</creatorcontrib><creatorcontrib>Tang, Yaohui</creatorcontrib><creatorcontrib>Yang, Guo-Yuan</creatorcontrib><creatorcontrib>Liu, Yingli</creatorcontrib><creatorcontrib>Zhang, Zhijun</creatorcontrib><title>Engineered exosomes mediated targeted delivery of neuroprotective peptide NR2B9c for the treatment of traumatic brain injury</title><title>International journal of pharmaceutics</title><addtitle>Int J Pharm</addtitle><description>Neuroprotection is one of the core treatment strategies for brain injuries including traumatic brain injury (TBI). NR2B9c is a promising neuroprotective peptide but its clinical translation is limited because of poor brain penetrability. Exosomes are naturally occurring nanovesicles having therapeutic potential for TBI as well as an efficient drug delivery carrier to the brain. Here, we engineered exosomes with neuron targeting peptide rabies virus glycoprotein (RVG29) via bio-orthogonal click chemistry technique and loaded it with NR2B9c, developing RVG-Exo
. RVG29 conjugated exosome had higher neuron targeting efficiency compared to naïve exosomes both in vivo and in vitro. RVG-Exo
had great cytoprotective effect against oxygen glucose deprived Neuro2a cells. Intravenous administration of RVG-Exo
significantly improved behavioral outcomes and reduced the lesion volume after TBI injury in a mice controlled cortical impact model. Due to their multifunctionality and significant efficacy, we anticipate that RVG-Exo
have the potential to be translated both as therapeutic agent as well as cargo delivery system to the brain for the treatment of TBI.</description><subject>Animals</subject><subject>Brain</subject><subject>Brain Injuries, Traumatic - drug therapy</subject><subject>Brain Injuries, Traumatic - pathology</subject><subject>Drug Carriers - pharmacology</subject><subject>Exosomes</subject><subject>Mice</subject><subject>Neuroprotection</subject><subject>Peptides</subject><issn>0378-5173</issn><issn>1873-3476</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kFtLxDAQhYMoul5-gpJHX7rm0jbJo4o3EAXR55Ck092U7cUkFRf88XbZ1acZDufMHD6EzimZU0LLq2bum2FpQjtnhPE5Zbwsyj00o1LwjOei3EczwoXMCir4ETqOsSGElIzyQ3TEJckJV2yGfu66he8AAlQYvvvYtxBxC5U3aVKSCQvYLBWs_BeENe5r3MEY-iH0CVyaRDzAkHwF-OWN3SiH6z7gtAScApjUQpc2mRTM2JrkHbbB-A77rhnD-hQd1GYV4Ww3T9DH_d377WP2_PrwdHv9nDlOVMqsdVYISyvqhHQVEVRIIwQopYocqtwW0qmam0qJwkpKilzkFnJpLC-oJTU_QZfbu1PrzxFi0q2PDlYr00E_Rs2kKiWRnLHJWmytLvQxBqj1EHxrwlpTojfgdaN34PUGvN6Cn3IXuxejnfD9p_5I818Q2YP5</recordid><startdate>20240105</startdate><enddate>20240105</enddate><creator>Haroon, Khan</creator><creator>Zheng, Haoran</creator><creator>Wu, Shengju</creator><creator>Liu, Ze</creator><creator>Tang, Yaohui</creator><creator>Yang, Guo-Yuan</creator><creator>Liu, Yingli</creator><creator>Zhang, Zhijun</creator><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>7X8</scope></search><sort><creationdate>20240105</creationdate><title>Engineered exosomes mediated targeted delivery of neuroprotective peptide NR2B9c for the treatment of traumatic brain injury</title><author>Haroon, Khan ; Zheng, Haoran ; Wu, Shengju ; Liu, Ze ; Tang, Yaohui ; Yang, Guo-Yuan ; Liu, Yingli ; Zhang, Zhijun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c309t-bbcb77b1d1c78cd07178a77e99954ed4b58c9f3ad975b8105474be48ab351b0f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animals</topic><topic>Brain</topic><topic>Brain Injuries, Traumatic - drug therapy</topic><topic>Brain Injuries, Traumatic - pathology</topic><topic>Drug Carriers - pharmacology</topic><topic>Exosomes</topic><topic>Mice</topic><topic>Neuroprotection</topic><topic>Peptides</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Haroon, Khan</creatorcontrib><creatorcontrib>Zheng, Haoran</creatorcontrib><creatorcontrib>Wu, Shengju</creatorcontrib><creatorcontrib>Liu, Ze</creatorcontrib><creatorcontrib>Tang, Yaohui</creatorcontrib><creatorcontrib>Yang, Guo-Yuan</creatorcontrib><creatorcontrib>Liu, Yingli</creatorcontrib><creatorcontrib>Zhang, Zhijun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of pharmaceutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Haroon, Khan</au><au>Zheng, Haoran</au><au>Wu, Shengju</au><au>Liu, Ze</au><au>Tang, Yaohui</au><au>Yang, Guo-Yuan</au><au>Liu, Yingli</au><au>Zhang, Zhijun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Engineered exosomes mediated targeted delivery of neuroprotective peptide NR2B9c for the treatment of traumatic brain injury</atitle><jtitle>International journal of pharmaceutics</jtitle><addtitle>Int J Pharm</addtitle><date>2024-01-05</date><risdate>2024</risdate><volume>649</volume><spage>123656</spage><epage>123656</epage><pages>123656-123656</pages><artnum>123656</artnum><issn>0378-5173</issn><eissn>1873-3476</eissn><abstract>Neuroprotection is one of the core treatment strategies for brain injuries including traumatic brain injury (TBI). NR2B9c is a promising neuroprotective peptide but its clinical translation is limited because of poor brain penetrability. Exosomes are naturally occurring nanovesicles having therapeutic potential for TBI as well as an efficient drug delivery carrier to the brain. Here, we engineered exosomes with neuron targeting peptide rabies virus glycoprotein (RVG29) via bio-orthogonal click chemistry technique and loaded it with NR2B9c, developing RVG-Exo
. RVG29 conjugated exosome had higher neuron targeting efficiency compared to naïve exosomes both in vivo and in vitro. RVG-Exo
had great cytoprotective effect against oxygen glucose deprived Neuro2a cells. Intravenous administration of RVG-Exo
significantly improved behavioral outcomes and reduced the lesion volume after TBI injury in a mice controlled cortical impact model. Due to their multifunctionality and significant efficacy, we anticipate that RVG-Exo
have the potential to be translated both as therapeutic agent as well as cargo delivery system to the brain for the treatment of TBI.</abstract><cop>Netherlands</cop><pmid>38040392</pmid><doi>10.1016/j.ijpharm.2023.123656</doi><tpages>1</tpages></addata></record> |
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subjects | Animals Brain Brain Injuries, Traumatic - drug therapy Brain Injuries, Traumatic - pathology Drug Carriers - pharmacology Exosomes Mice Neuroprotection Peptides |
title | Engineered exosomes mediated targeted delivery of neuroprotective peptide NR2B9c for the treatment of traumatic brain injury |
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