Virus-like particles with removable cyclodextrins enable glutathione-triggered drug release in cells
The efficient delivery of hydrophobic drugs into target cells without the use of organic solvents or chemical linkage to delivery carriers is an important theme in the biomedical and pharmaceutical field. In this study, we synthesized virus-like particles (VLPs) coupled with cyclodextrins (CDs) as h...
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| Veröffentlicht in: | Molecular bioSystems 2013-03, Vol.9 (3), p.51-57 |
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| creator | Niikura, Kenichi Sugimura, Naotoshi Musashi, Yusuke Mikuni, Shintaro Matsuo, Yasutaka Kobayashi, Shintaro Nagakawa, Keita Takahara, Shuko Takeuchi, Chie Sawa, Hirofumi Kinjo, Masataka Ijiro, Kuniharu |
| description | The efficient delivery of hydrophobic drugs into target cells without the use of organic solvents or chemical linkage to delivery carriers is an important theme in the biomedical and pharmaceutical field. In this study, we synthesized virus-like particles (VLPs) coupled with cyclodextrins (CDs) as hydrophobic pockets through disulfide bonds inside the VLPs, where hydrophobic drugs can be incorporated. We report here the intracellular delivery of hydrophobic dyes or drugs encapsulated in VLPs through CDs with high efficiency and their subsequent release in cells in response to glutathione. As a model anticancer drug, paclitaxel (PTX)-CD complexes were encapsulated inside VLPs and the cytotoxic drug activity of PTX loaded VLPs against NIH3T3 cells was evaluated by CCK-8 assay. PTX-loaded VLPs exhibited a dose-dependent cytotoxic effect with a 20-fold smaller IC
50
than that of free PTX dissolved in DMSO. These results indicate that VLPs with removable CDs afford highly promising carriers of hydrophobic drugs without chemical modification of drugs.
Virus-like particles enabling the glutathione-triggered release of hydrophobic drugs in cells. |
| doi_str_mv | 10.1039/c2mb25420d |
| format | Article |
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50
than that of free PTX dissolved in DMSO. These results indicate that VLPs with removable CDs afford highly promising carriers of hydrophobic drugs without chemical modification of drugs.
Virus-like particles enabling the glutathione-triggered release of hydrophobic drugs in cells.</description><identifier>ISSN: 1742-206X</identifier><identifier>EISSN: 1742-2051</identifier><identifier>DOI: 10.1039/c2mb25420d</identifier><identifier>PMID: 23361582</identifier><language>eng</language><publisher>England</publisher><subject>Adamantane - chemistry ; Adamantane - metabolism ; Animals ; Antineoplastic Agents, Phytogenic - metabolism ; Antineoplastic Agents, Phytogenic - pharmacology ; Antitumor agents ; Boron Compounds - chemistry ; Boron Compounds - metabolism ; Cell Survival - drug effects ; Chemical modification ; cyclodextrin ; Cyclodextrins - chemistry ; Cyclodextrins - metabolism ; Cytotoxicity ; Disulfide bonds ; Drug delivery ; Drugs ; Dyes ; Fluorescent Dyes - chemistry ; Fluorescent Dyes - metabolism ; Glutathione ; Glutathione - pharmacology ; Hydrophobic and Hydrophilic Interactions ; Hydrophobicity ; Inhibitory Concentration 50 ; JC Virus - chemistry ; Mice ; Nanocapsules - chemistry ; Nanocapsules - ultrastructure ; NIH 3T3 Cells ; Paclitaxel ; Paclitaxel - metabolism ; Paclitaxel - pharmacology ; Particle Size ; Pharmaceuticals ; Rhodamines - chemistry ; Rhodamines - metabolism ; Solvents ; Virion - chemistry ; Virion - metabolism ; Virus-like particles</subject><ispartof>Molecular bioSystems, 2013-03, Vol.9 (3), p.51-57</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c368t-c6236159543a84b58acf35a68a93afdee544c30a6b551855ea0b76e79a3600283</citedby><cites>FETCH-LOGICAL-c368t-c6236159543a84b58acf35a68a93afdee544c30a6b551855ea0b76e79a3600283</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23361582$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Niikura, Kenichi</creatorcontrib><creatorcontrib>Sugimura, Naotoshi</creatorcontrib><creatorcontrib>Musashi, Yusuke</creatorcontrib><creatorcontrib>Mikuni, Shintaro</creatorcontrib><creatorcontrib>Matsuo, Yasutaka</creatorcontrib><creatorcontrib>Kobayashi, Shintaro</creatorcontrib><creatorcontrib>Nagakawa, Keita</creatorcontrib><creatorcontrib>Takahara, Shuko</creatorcontrib><creatorcontrib>Takeuchi, Chie</creatorcontrib><creatorcontrib>Sawa, Hirofumi</creatorcontrib><creatorcontrib>Kinjo, Masataka</creatorcontrib><creatorcontrib>Ijiro, Kuniharu</creatorcontrib><title>Virus-like particles with removable cyclodextrins enable glutathione-triggered drug release in cells</title><title>Molecular bioSystems</title><addtitle>Mol Biosyst</addtitle><description>The efficient delivery of hydrophobic drugs into target cells without the use of organic solvents or chemical linkage to delivery carriers is an important theme in the biomedical and pharmaceutical field. In this study, we synthesized virus-like particles (VLPs) coupled with cyclodextrins (CDs) as hydrophobic pockets through disulfide bonds inside the VLPs, where hydrophobic drugs can be incorporated. We report here the intracellular delivery of hydrophobic dyes or drugs encapsulated in VLPs through CDs with high efficiency and their subsequent release in cells in response to glutathione. As a model anticancer drug, paclitaxel (PTX)-CD complexes were encapsulated inside VLPs and the cytotoxic drug activity of PTX loaded VLPs against NIH3T3 cells was evaluated by CCK-8 assay. PTX-loaded VLPs exhibited a dose-dependent cytotoxic effect with a 20-fold smaller IC
50
than that of free PTX dissolved in DMSO. These results indicate that VLPs with removable CDs afford highly promising carriers of hydrophobic drugs without chemical modification of drugs.
Virus-like particles enabling the glutathione-triggered release of hydrophobic drugs in cells.</description><subject>Adamantane - chemistry</subject><subject>Adamantane - metabolism</subject><subject>Animals</subject><subject>Antineoplastic Agents, Phytogenic - metabolism</subject><subject>Antineoplastic Agents, Phytogenic - pharmacology</subject><subject>Antitumor agents</subject><subject>Boron Compounds - chemistry</subject><subject>Boron Compounds - metabolism</subject><subject>Cell Survival - drug effects</subject><subject>Chemical modification</subject><subject>cyclodextrin</subject><subject>Cyclodextrins - chemistry</subject><subject>Cyclodextrins - metabolism</subject><subject>Cytotoxicity</subject><subject>Disulfide bonds</subject><subject>Drug delivery</subject><subject>Drugs</subject><subject>Dyes</subject><subject>Fluorescent Dyes - chemistry</subject><subject>Fluorescent Dyes - metabolism</subject><subject>Glutathione</subject><subject>Glutathione - pharmacology</subject><subject>Hydrophobic and Hydrophilic Interactions</subject><subject>Hydrophobicity</subject><subject>Inhibitory Concentration 50</subject><subject>JC Virus - chemistry</subject><subject>Mice</subject><subject>Nanocapsules - chemistry</subject><subject>Nanocapsules - ultrastructure</subject><subject>NIH 3T3 Cells</subject><subject>Paclitaxel</subject><subject>Paclitaxel - metabolism</subject><subject>Paclitaxel - pharmacology</subject><subject>Particle Size</subject><subject>Pharmaceuticals</subject><subject>Rhodamines - chemistry</subject><subject>Rhodamines - metabolism</subject><subject>Solvents</subject><subject>Virion - chemistry</subject><subject>Virion - metabolism</subject><subject>Virus-like particles</subject><issn>1742-206X</issn><issn>1742-2051</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0T1PwzAQBmALgSgUFnZQ2BBSwN91RlTxJVViAcQWOc4lNThJsROg_56UlnaDyZbv8avTHUJHBF8QzJJLQ6uMCk5xvoX2yIjTmGJBttd3-TJA-yG8YswUJ3gXDShjkghF91D-bH0XYmffIJpp31rjIESftp1GHqrmQ2cOIjM3rsnhq_W2DhHUP4-l61rdTm1TQ9wXyhI85FHuu7L_6UAHiGwdGXAuHKCdQrsAh6tziJ5urh_Hd_Hk4fZ-fDWJDZOqjY2ki7YSwZlWPBNKm4IJLZVOmC5yAMG5YVjLTAiihACNs5GEUaKZxJgqNkRny9yZb947CG1a2bDoQNfQdCEljAiJZcL5_5QqLikXI9HT8yU1vgnBQ5HOvK20n6cEp4sFpJsF9PhkldtlFeRr-jvxHpwugQ9mXd0EpLO86M3xX4Z9A1YDltE</recordid><startdate>201303</startdate><enddate>201303</enddate><creator>Niikura, Kenichi</creator><creator>Sugimura, Naotoshi</creator><creator>Musashi, Yusuke</creator><creator>Mikuni, Shintaro</creator><creator>Matsuo, Yasutaka</creator><creator>Kobayashi, Shintaro</creator><creator>Nagakawa, Keita</creator><creator>Takahara, Shuko</creator><creator>Takeuchi, Chie</creator><creator>Sawa, Hirofumi</creator><creator>Kinjo, Masataka</creator><creator>Ijiro, Kuniharu</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><scope>7U9</scope><scope>H94</scope></search><sort><creationdate>201303</creationdate><title>Virus-like particles with removable cyclodextrins enable glutathione-triggered drug release in cells</title><author>Niikura, Kenichi ; Sugimura, Naotoshi ; Musashi, Yusuke ; Mikuni, Shintaro ; Matsuo, Yasutaka ; Kobayashi, Shintaro ; Nagakawa, Keita ; Takahara, Shuko ; Takeuchi, Chie ; Sawa, Hirofumi ; Kinjo, Masataka ; Ijiro, Kuniharu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c368t-c6236159543a84b58acf35a68a93afdee544c30a6b551855ea0b76e79a3600283</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adamantane - chemistry</topic><topic>Adamantane - metabolism</topic><topic>Animals</topic><topic>Antineoplastic Agents, Phytogenic - metabolism</topic><topic>Antineoplastic Agents, Phytogenic - pharmacology</topic><topic>Antitumor agents</topic><topic>Boron Compounds - chemistry</topic><topic>Boron Compounds - metabolism</topic><topic>Cell Survival - drug effects</topic><topic>Chemical modification</topic><topic>cyclodextrin</topic><topic>Cyclodextrins - chemistry</topic><topic>Cyclodextrins - metabolism</topic><topic>Cytotoxicity</topic><topic>Disulfide bonds</topic><topic>Drug delivery</topic><topic>Drugs</topic><topic>Dyes</topic><topic>Fluorescent Dyes - chemistry</topic><topic>Fluorescent Dyes - metabolism</topic><topic>Glutathione</topic><topic>Glutathione - pharmacology</topic><topic>Hydrophobic and Hydrophilic Interactions</topic><topic>Hydrophobicity</topic><topic>Inhibitory Concentration 50</topic><topic>JC Virus - chemistry</topic><topic>Mice</topic><topic>Nanocapsules - chemistry</topic><topic>Nanocapsules - ultrastructure</topic><topic>NIH 3T3 Cells</topic><topic>Paclitaxel</topic><topic>Paclitaxel - metabolism</topic><topic>Paclitaxel - pharmacology</topic><topic>Particle Size</topic><topic>Pharmaceuticals</topic><topic>Rhodamines - chemistry</topic><topic>Rhodamines - metabolism</topic><topic>Solvents</topic><topic>Virion - chemistry</topic><topic>Virion - metabolism</topic><topic>Virus-like particles</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Niikura, Kenichi</creatorcontrib><creatorcontrib>Sugimura, Naotoshi</creatorcontrib><creatorcontrib>Musashi, Yusuke</creatorcontrib><creatorcontrib>Mikuni, Shintaro</creatorcontrib><creatorcontrib>Matsuo, Yasutaka</creatorcontrib><creatorcontrib>Kobayashi, Shintaro</creatorcontrib><creatorcontrib>Nagakawa, Keita</creatorcontrib><creatorcontrib>Takahara, Shuko</creatorcontrib><creatorcontrib>Takeuchi, Chie</creatorcontrib><creatorcontrib>Sawa, Hirofumi</creatorcontrib><creatorcontrib>Kinjo, Masataka</creatorcontrib><creatorcontrib>Ijiro, Kuniharu</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><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Molecular bioSystems</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Niikura, Kenichi</au><au>Sugimura, Naotoshi</au><au>Musashi, Yusuke</au><au>Mikuni, Shintaro</au><au>Matsuo, Yasutaka</au><au>Kobayashi, Shintaro</au><au>Nagakawa, Keita</au><au>Takahara, Shuko</au><au>Takeuchi, Chie</au><au>Sawa, Hirofumi</au><au>Kinjo, Masataka</au><au>Ijiro, Kuniharu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Virus-like particles with removable cyclodextrins enable glutathione-triggered drug release in cells</atitle><jtitle>Molecular bioSystems</jtitle><addtitle>Mol Biosyst</addtitle><date>2013-03</date><risdate>2013</risdate><volume>9</volume><issue>3</issue><spage>51</spage><epage>57</epage><pages>51-57</pages><issn>1742-206X</issn><eissn>1742-2051</eissn><abstract>The efficient delivery of hydrophobic drugs into target cells without the use of organic solvents or chemical linkage to delivery carriers is an important theme in the biomedical and pharmaceutical field. In this study, we synthesized virus-like particles (VLPs) coupled with cyclodextrins (CDs) as hydrophobic pockets through disulfide bonds inside the VLPs, where hydrophobic drugs can be incorporated. We report here the intracellular delivery of hydrophobic dyes or drugs encapsulated in VLPs through CDs with high efficiency and their subsequent release in cells in response to glutathione. As a model anticancer drug, paclitaxel (PTX)-CD complexes were encapsulated inside VLPs and the cytotoxic drug activity of PTX loaded VLPs against NIH3T3 cells was evaluated by CCK-8 assay. PTX-loaded VLPs exhibited a dose-dependent cytotoxic effect with a 20-fold smaller IC
50
than that of free PTX dissolved in DMSO. These results indicate that VLPs with removable CDs afford highly promising carriers of hydrophobic drugs without chemical modification of drugs.
Virus-like particles enabling the glutathione-triggered release of hydrophobic drugs in cells.</abstract><cop>England</cop><pmid>23361582</pmid><doi>10.1039/c2mb25420d</doi><tpages>7</tpages></addata></record> |
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| ispartof | Molecular bioSystems, 2013-03, Vol.9 (3), p.51-57 |
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| subjects | Adamantane - chemistry Adamantane - metabolism Animals Antineoplastic Agents, Phytogenic - metabolism Antineoplastic Agents, Phytogenic - pharmacology Antitumor agents Boron Compounds - chemistry Boron Compounds - metabolism Cell Survival - drug effects Chemical modification cyclodextrin Cyclodextrins - chemistry Cyclodextrins - metabolism Cytotoxicity Disulfide bonds Drug delivery Drugs Dyes Fluorescent Dyes - chemistry Fluorescent Dyes - metabolism Glutathione Glutathione - pharmacology Hydrophobic and Hydrophilic Interactions Hydrophobicity Inhibitory Concentration 50 JC Virus - chemistry Mice Nanocapsules - chemistry Nanocapsules - ultrastructure NIH 3T3 Cells Paclitaxel Paclitaxel - metabolism Paclitaxel - pharmacology Particle Size Pharmaceuticals Rhodamines - chemistry Rhodamines - metabolism Solvents Virion - chemistry Virion - metabolism Virus-like particles |
| title | Virus-like particles with removable cyclodextrins enable glutathione-triggered drug release in cells |
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