Enhanced Therapeutic Efficacy of iRGD-Conjugated Crosslinked Multilayer Liposomes for Drug Delivery
Targeting nanoparticles by conjugating various specific ligands has shown potential therapeutic efficacy in nanomedicine. However, poor penetration of antitumor drugs into solid tumors remains a major obstacle. Here, we describe a targeting strategy for antitumor drug delivery by conjugating a cross...
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| Veröffentlicht in: | BioMed research international 2013-01, Vol.2013 (2013), p.1-11 |
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| creator | Joo, Kye-Il Wong, Michael K. Ji, Man Liu, Yarong Wang, Pin |
| description | Targeting nanoparticles by conjugating various specific ligands has shown potential therapeutic efficacy in nanomedicine. However, poor penetration of antitumor drugs into solid tumors remains a major obstacle. Here, we describe a targeting strategy for antitumor drug delivery by conjugating a crosslinked multilamellar liposomal vesicle (cMLV) formulation with a tumor-penetrating peptide, iRGD. The results showed that iRGD peptides could facilitate the binding and cellular uptake of drug-loaded cMLVs and consequently enhance the antitumor efficacy in breast tumor cells, including multidrug-resistant cells. Moreover, colocalization data revealed that iRGD-conjugated cMLVs (iRGD-cMLVs) entered cells via the clathrin-mediated pathway, followed by endosome-lysosome transport for efficient drug delivery. Finally, in vivo study indicated that iRGD-cMLVs could deliver anticancer drugs efficiently to mediate significant tumor suppression. |
| doi_str_mv | 10.1155/2013/378380 |
| format | Article |
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However, poor penetration of antitumor drugs into solid tumors remains a major obstacle. Here, we describe a targeting strategy for antitumor drug delivery by conjugating a crosslinked multilamellar liposomal vesicle (cMLV) formulation with a tumor-penetrating peptide, iRGD. The results showed that iRGD peptides could facilitate the binding and cellular uptake of drug-loaded cMLVs and consequently enhance the antitumor efficacy in breast tumor cells, including multidrug-resistant cells. Moreover, colocalization data revealed that iRGD-conjugated cMLVs (iRGD-cMLVs) entered cells via the clathrin-mediated pathway, followed by endosome-lysosome transport for efficient drug delivery. Finally, in vivo study indicated that iRGD-cMLVs could deliver anticancer drugs efficiently to mediate significant tumor suppression.</description><identifier>ISSN: 2314-6133</identifier><identifier>EISSN: 2314-6141</identifier><identifier>DOI: 10.1155/2013/378380</identifier><identifier>PMID: 23691500</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Publishing Corporation</publisher><subject>Animals ; Cell Death - drug effects ; Cell Line, Tumor ; Clathrin - metabolism ; Cross-Linking Reagents - chemistry ; Disease Models, Animal ; Doxorubicin - pharmacology ; Doxorubicin - therapeutic use ; Drug Delivery Systems ; Drugs ; Endocytosis - drug effects ; Endosomes - drug effects ; Endosomes - metabolism ; Evaluation ; Female ; Gene therapy ; Humans ; Intracellular Space - metabolism ; Liposomes ; Lysosomes - drug effects ; Lysosomes - metabolism ; Mammary Neoplasms, Animal - drug therapy ; Mice ; Mice, Inbred BALB C ; Oligopeptides - chemistry ; Oligopeptides - pharmacology ; Oligopeptides - therapeutic use ; Oligopeptides - toxicity ; Treatment Outcome ; Vehicles</subject><ispartof>BioMed research international, 2013-01, Vol.2013 (2013), p.1-11</ispartof><rights>Copyright © 2013 Yarong Liu et al.</rights><rights>COPYRIGHT 2013 John Wiley & Sons, Inc.</rights><rights>Copyright © 2013 Yarong Liu et al. 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c467t-5408a1dd15387fba8945d0a45cbddc55f2b646f943a49c3d1d3a156655c733c43</citedby><cites>FETCH-LOGICAL-c467t-5408a1dd15387fba8945d0a45cbddc55f2b646f943a49c3d1d3a156655c733c43</cites><orcidid>0000-0002-4132-105X</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/PMC3652104/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3652104/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23691500$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Valduga, Claudete J.</contributor><creatorcontrib>Joo, Kye-Il</creatorcontrib><creatorcontrib>Wong, Michael K.</creatorcontrib><creatorcontrib>Ji, Man</creatorcontrib><creatorcontrib>Liu, Yarong</creatorcontrib><creatorcontrib>Wang, Pin</creatorcontrib><title>Enhanced Therapeutic Efficacy of iRGD-Conjugated Crosslinked Multilayer Liposomes for Drug Delivery</title><title>BioMed research international</title><addtitle>Biomed Res Int</addtitle><description>Targeting nanoparticles by conjugating various specific ligands has shown potential therapeutic efficacy in nanomedicine. However, poor penetration of antitumor drugs into solid tumors remains a major obstacle. Here, we describe a targeting strategy for antitumor drug delivery by conjugating a crosslinked multilamellar liposomal vesicle (cMLV) formulation with a tumor-penetrating peptide, iRGD. The results showed that iRGD peptides could facilitate the binding and cellular uptake of drug-loaded cMLVs and consequently enhance the antitumor efficacy in breast tumor cells, including multidrug-resistant cells. Moreover, colocalization data revealed that iRGD-conjugated cMLVs (iRGD-cMLVs) entered cells via the clathrin-mediated pathway, followed by endosome-lysosome transport for efficient drug delivery. Finally, in vivo study indicated that iRGD-cMLVs could deliver anticancer drugs efficiently to mediate significant tumor suppression.</description><subject>Animals</subject><subject>Cell Death - drug effects</subject><subject>Cell Line, Tumor</subject><subject>Clathrin - metabolism</subject><subject>Cross-Linking Reagents - chemistry</subject><subject>Disease Models, Animal</subject><subject>Doxorubicin - pharmacology</subject><subject>Doxorubicin - therapeutic use</subject><subject>Drug Delivery Systems</subject><subject>Drugs</subject><subject>Endocytosis - drug effects</subject><subject>Endosomes - drug effects</subject><subject>Endosomes - metabolism</subject><subject>Evaluation</subject><subject>Female</subject><subject>Gene therapy</subject><subject>Humans</subject><subject>Intracellular Space - metabolism</subject><subject>Liposomes</subject><subject>Lysosomes - drug effects</subject><subject>Lysosomes - metabolism</subject><subject>Mammary Neoplasms, Animal - drug therapy</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Oligopeptides - chemistry</subject><subject>Oligopeptides - pharmacology</subject><subject>Oligopeptides - therapeutic use</subject><subject>Oligopeptides - toxicity</subject><subject>Treatment Outcome</subject><subject>Vehicles</subject><issn>2314-6133</issn><issn>2314-6141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>EIF</sourceid><recordid>eNqN0c-L1DAUB_Agiruse_IuBW9K3by-JG0vwjIzrsKIIOs5vMmPmaydZkjblfnvzVAd1pu5JJAP3xfyZew18A8AUt5UHPAG6wYb_oxdVgiiVCDg-fmMeMGuh-GB59WA4q16yS4qVC1Izi-ZWfU76o2zxf3OJTq4aQymWHkfDJljEX0Rvt8ty0XsH6YtjdktUhyGLvQ_8_nr1I2ho6NLxToc4hD3bih8TMUyTdti6brw6NLxFXvhqRvc9Z_9iv34tLpffC7X3-6-LG7XpRGqHkspeENgLUhsar-hphXSchLSbKw1Uvpqo4TyrUASrUELFgmkUlKaGtEIvGIf59zDtNk7a1w_Jur0IYU9paOOFPS_N33Y6W181KhkBfwU8HYO2FLndOh9zMzsw2D0LeYZdaVqyOr9rMzpJ5Lz5wnA9akUfSpFz6Vk_ebpo872bwUZvJvBLvSWfoX_S3OZOE9PMBcgJP4G9Syd7A</recordid><startdate>20130101</startdate><enddate>20130101</enddate><creator>Joo, Kye-Il</creator><creator>Wong, Michael K.</creator><creator>Ji, Man</creator><creator>Liu, Yarong</creator><creator>Wang, Pin</creator><general>Hindawi Publishing Corporation</general><general>John Wiley & Sons, Inc</general><scope>ADJCN</scope><scope>AHFXO</scope><scope>RHU</scope><scope>RHW</scope><scope>RHX</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>5PM</scope><orcidid>https://orcid.org/0000-0002-4132-105X</orcidid></search><sort><creationdate>20130101</creationdate><title>Enhanced Therapeutic Efficacy of iRGD-Conjugated Crosslinked Multilayer Liposomes for Drug Delivery</title><author>Joo, Kye-Il ; 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However, poor penetration of antitumor drugs into solid tumors remains a major obstacle. Here, we describe a targeting strategy for antitumor drug delivery by conjugating a crosslinked multilamellar liposomal vesicle (cMLV) formulation with a tumor-penetrating peptide, iRGD. The results showed that iRGD peptides could facilitate the binding and cellular uptake of drug-loaded cMLVs and consequently enhance the antitumor efficacy in breast tumor cells, including multidrug-resistant cells. Moreover, colocalization data revealed that iRGD-conjugated cMLVs (iRGD-cMLVs) entered cells via the clathrin-mediated pathway, followed by endosome-lysosome transport for efficient drug delivery. 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| subjects | Animals Cell Death - drug effects Cell Line, Tumor Clathrin - metabolism Cross-Linking Reagents - chemistry Disease Models, Animal Doxorubicin - pharmacology Doxorubicin - therapeutic use Drug Delivery Systems Drugs Endocytosis - drug effects Endosomes - drug effects Endosomes - metabolism Evaluation Female Gene therapy Humans Intracellular Space - metabolism Liposomes Lysosomes - drug effects Lysosomes - metabolism Mammary Neoplasms, Animal - drug therapy Mice Mice, Inbred BALB C Oligopeptides - chemistry Oligopeptides - pharmacology Oligopeptides - therapeutic use Oligopeptides - toxicity Treatment Outcome Vehicles |
| title | Enhanced Therapeutic Efficacy of iRGD-Conjugated Crosslinked Multilayer Liposomes for Drug Delivery |
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