Light‐Inducible Exosome‐Based Vehicle for Endogenous RNA Loading and Delivery to Leukemia Cells
Exosomes are a novel and promising drug delivery platform because of their endogenous origin, stability, biocompatibility, and other unique features. As the efficient loading and delivery of long RNA to target cells for therapeutic purposes remains challenging, a new exosome‐based RNA delivery syste...
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Veröffentlicht in: | Advanced functional materials 2019-02, Vol.29 (9), p.n/a |
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description | Exosomes are a novel and promising drug delivery platform because of their endogenous origin, stability, biocompatibility, and other unique features. As the efficient loading and delivery of long RNA to target cells for therapeutic purposes remains challenging, a new exosome‐based RNA delivery system is proposed using a controllable RNA enrichment and releasing protocol. The system employs RNA aptamer–protein interactions and reversible light‐inducible protein–protein interaction modules by remolding exosome producer cells. Endogenous microRNA 21 (miR‐21) sponges, inhibitors of miR‐21, are successfully enriched on the plasma membrane and are sorted into exosomes by the biogenesis of the exosomes. The loading capacity of miR‐21 sponges is enhanced by 14‐fold in the light‐inducible loading system. In addition, targeted delivery of miR‐21 to leukemia cells is achieved by modifying exosomes with the cholesterol‐conjugated aptamer AS1411, resulting in significant cell apoptosis by blocking the function of miR‐21 in leukemia cells. This work provides an exosome‐based light‐inducible vehicle to efficiently load and deliver long endogenous RNA, which can enable more RNA‐based therapeutics for personalized cancer medicine.
Exosomes are a novel and promising method for drug delivery. Here, a new exosome‐based light‐inducible vehicle is constructed through multiple molecular engineering and a blue light controllable RNA enrichment/releasing protocol. This system can efficiently load and deliver a long endogenous miRNA‐based agent (such as miRNA‐21 sponges) to target tumor cells, and thus regulate the expression of target protein of miRNA. |
doi_str_mv | 10.1002/adfm.201807189 |
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Exosomes are a novel and promising method for drug delivery. Here, a new exosome‐based light‐inducible vehicle is constructed through multiple molecular engineering and a blue light controllable RNA enrichment/releasing protocol. This system can efficiently load and deliver a long endogenous miRNA‐based agent (such as miRNA‐21 sponges) to target tumor cells, and thus regulate the expression of target protein of miRNA.</description><identifier>ISSN: 1616-301X</identifier><identifier>EISSN: 1616-3028</identifier><identifier>DOI: 10.1002/adfm.201807189</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc</publisher><subject>Apoptosis ; aptamers ; Biocompatibility ; Cholesterol ; Drug delivery systems ; exosomes ; Leukemia ; Materials science ; miRNA sponge ; Proteins ; reversible light‐inducible vehicles ; Ribonucleic acid ; RNA ; RNA enrichment ; Sponges</subject><ispartof>Advanced functional materials, 2019-02, Vol.29 (9), p.n/a</ispartof><rights>2019 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3839-bbe8c23c42a66357225f9d35d7005a3911c46e7f80578c3d7ebc7fc40a5e2dc83</citedby><cites>FETCH-LOGICAL-c3839-bbe8c23c42a66357225f9d35d7005a3911c46e7f80578c3d7ebc7fc40a5e2dc83</cites><orcidid>0000-0003-1347-3168</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fadfm.201807189$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fadfm.201807189$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids></links><search><creatorcontrib>Huang, Lin</creatorcontrib><creatorcontrib>Gu, Ning</creatorcontrib><creatorcontrib>Zhang, Xian‐En</creatorcontrib><creatorcontrib>Wang, Dian‐Bing</creatorcontrib><title>Light‐Inducible Exosome‐Based Vehicle for Endogenous RNA Loading and Delivery to Leukemia Cells</title><title>Advanced functional materials</title><description>Exosomes are a novel and promising drug delivery platform because of their endogenous origin, stability, biocompatibility, and other unique features. As the efficient loading and delivery of long RNA to target cells for therapeutic purposes remains challenging, a new exosome‐based RNA delivery system is proposed using a controllable RNA enrichment and releasing protocol. The system employs RNA aptamer–protein interactions and reversible light‐inducible protein–protein interaction modules by remolding exosome producer cells. Endogenous microRNA 21 (miR‐21) sponges, inhibitors of miR‐21, are successfully enriched on the plasma membrane and are sorted into exosomes by the biogenesis of the exosomes. The loading capacity of miR‐21 sponges is enhanced by 14‐fold in the light‐inducible loading system. In addition, targeted delivery of miR‐21 to leukemia cells is achieved by modifying exosomes with the cholesterol‐conjugated aptamer AS1411, resulting in significant cell apoptosis by blocking the function of miR‐21 in leukemia cells. This work provides an exosome‐based light‐inducible vehicle to efficiently load and deliver long endogenous RNA, which can enable more RNA‐based therapeutics for personalized cancer medicine.
Exosomes are a novel and promising method for drug delivery. Here, a new exosome‐based light‐inducible vehicle is constructed through multiple molecular engineering and a blue light controllable RNA enrichment/releasing protocol. This system can efficiently load and deliver a long endogenous miRNA‐based agent (such as miRNA‐21 sponges) to target tumor cells, and thus regulate the expression of target protein of miRNA.</description><subject>Apoptosis</subject><subject>aptamers</subject><subject>Biocompatibility</subject><subject>Cholesterol</subject><subject>Drug delivery systems</subject><subject>exosomes</subject><subject>Leukemia</subject><subject>Materials science</subject><subject>miRNA sponge</subject><subject>Proteins</subject><subject>reversible light‐inducible vehicles</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA enrichment</subject><subject>Sponges</subject><issn>1616-301X</issn><issn>1616-3028</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNqFkMtOwzAQRS0EEqWwZW2JdYofSewsSx9QKYCEALGzHHvSpiRxiRugOz6Bb-RLSFUES1YzujpnRroInVIyoISwc23zasAIlURQmeyhHo1pHHDC5P7vTp8O0ZH3S0KoEDzsIZMW88X66-NzVtvWFFkJePLuvKugyy60B4sfYVGYLs9dgye1dXOoXevx3c0Qp07bop5jXVs8hrJ4hWaD1w6n0D5DVWg8grL0x-gg16WHk5_ZRw_Tyf3oKkhvL2ejYRoYLnkSZBlIw7gJmY5jHgnGojyxPLKCkEjzhFITxiBySSIhDbcCMiNyExIdAbNG8j46291dNe6lBb9WS9c2dfdSMSpjSsOExh012FGmcd43kKtVU1S62ShK1LZItS1S_RbZCclOeCtK2PxDq-F4ev3nfgMif3jg</recordid><startdate>20190228</startdate><enddate>20190228</enddate><creator>Huang, Lin</creator><creator>Gu, Ning</creator><creator>Zhang, Xian‐En</creator><creator>Wang, Dian‐Bing</creator><general>Wiley Subscription Services, Inc</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7SP</scope><scope>7SR</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>L7M</scope><orcidid>https://orcid.org/0000-0003-1347-3168</orcidid></search><sort><creationdate>20190228</creationdate><title>Light‐Inducible Exosome‐Based Vehicle for Endogenous RNA Loading and Delivery to Leukemia Cells</title><author>Huang, Lin ; Gu, Ning ; Zhang, Xian‐En ; Wang, Dian‐Bing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3839-bbe8c23c42a66357225f9d35d7005a3911c46e7f80578c3d7ebc7fc40a5e2dc83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Apoptosis</topic><topic>aptamers</topic><topic>Biocompatibility</topic><topic>Cholesterol</topic><topic>Drug delivery systems</topic><topic>exosomes</topic><topic>Leukemia</topic><topic>Materials science</topic><topic>miRNA sponge</topic><topic>Proteins</topic><topic>reversible light‐inducible vehicles</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA enrichment</topic><topic>Sponges</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Huang, Lin</creatorcontrib><creatorcontrib>Gu, Ning</creatorcontrib><creatorcontrib>Zhang, Xian‐En</creatorcontrib><creatorcontrib>Wang, Dian‐Bing</creatorcontrib><collection>CrossRef</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><jtitle>Advanced functional materials</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Huang, Lin</au><au>Gu, Ning</au><au>Zhang, Xian‐En</au><au>Wang, Dian‐Bing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Light‐Inducible Exosome‐Based Vehicle for Endogenous RNA Loading and Delivery to Leukemia Cells</atitle><jtitle>Advanced functional materials</jtitle><date>2019-02-28</date><risdate>2019</risdate><volume>29</volume><issue>9</issue><epage>n/a</epage><issn>1616-301X</issn><eissn>1616-3028</eissn><abstract>Exosomes are a novel and promising drug delivery platform because of their endogenous origin, stability, biocompatibility, and other unique features. As the efficient loading and delivery of long RNA to target cells for therapeutic purposes remains challenging, a new exosome‐based RNA delivery system is proposed using a controllable RNA enrichment and releasing protocol. The system employs RNA aptamer–protein interactions and reversible light‐inducible protein–protein interaction modules by remolding exosome producer cells. Endogenous microRNA 21 (miR‐21) sponges, inhibitors of miR‐21, are successfully enriched on the plasma membrane and are sorted into exosomes by the biogenesis of the exosomes. The loading capacity of miR‐21 sponges is enhanced by 14‐fold in the light‐inducible loading system. In addition, targeted delivery of miR‐21 to leukemia cells is achieved by modifying exosomes with the cholesterol‐conjugated aptamer AS1411, resulting in significant cell apoptosis by blocking the function of miR‐21 in leukemia cells. This work provides an exosome‐based light‐inducible vehicle to efficiently load and deliver long endogenous RNA, which can enable more RNA‐based therapeutics for personalized cancer medicine.
Exosomes are a novel and promising method for drug delivery. Here, a new exosome‐based light‐inducible vehicle is constructed through multiple molecular engineering and a blue light controllable RNA enrichment/releasing protocol. This system can efficiently load and deliver a long endogenous miRNA‐based agent (such as miRNA‐21 sponges) to target tumor cells, and thus regulate the expression of target protein of miRNA.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc</pub><doi>10.1002/adfm.201807189</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-1347-3168</orcidid></addata></record> |
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subjects | Apoptosis aptamers Biocompatibility Cholesterol Drug delivery systems exosomes Leukemia Materials science miRNA sponge Proteins reversible light‐inducible vehicles Ribonucleic acid RNA RNA enrichment Sponges |
title | Light‐Inducible Exosome‐Based Vehicle for Endogenous RNA Loading and Delivery to Leukemia Cells |
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