MicroRNA Biogenesis is Enhanced by Liposome-Encapsulated Pin1 Inhibitor in Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is in an urgent need of new, effective therapies to reduce morbidity and mortality. We have previously demonstrated that peptidyl-prolyl cis/trans isomerase Pin1 is a potential target for HCC therapy, due to its pivotal role in HCC development through regulating miRNA...
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| Veröffentlicht in: | Theranostics 2019-01, Vol.9 (16), p.4704-4716 |
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| creator | Sun, Dan Tan, Shuangyan Xiong, Yanli Pu, Wenchen Li, Jiao Wei, Wei Huang, Canhua Wei, Yu-Quan Peng, Yong |
| description | Hepatocellular carcinoma (HCC) is in an urgent need of new, effective therapies to reduce morbidity and mortality. We have previously demonstrated that peptidyl-prolyl cis/trans isomerase Pin1 is a potential target for HCC therapy, due to its pivotal role in HCC development through regulating miRNA biogenesis, and discovered the small molecule API-1 as a novel and specific Pin1 inhibitor. Despite its significant anti-HCC activity, the low water solubility and
bioavailability of API-1 limit its clinical application. To address these issues, we herein developed a liposomal formulation of API-1 to improve API-1 delivery and enhance its anti-HCC efficacy.
: We designed and developed a nanoscale liposomal formulation of API-1, named as API-LP. Subsequently, the mean diameter, polydispersity, zeta potential, encapsulation efficiency and thermal properties of the optimization API-LP were characterized. The enhanced anti-HCC activity and the molecular mechanism of API-LP were investigated both
and
. Finally, the safety and pharmacokinetic property of API-LP were evaluated systematically.
: API-LP had good formulation characteristics and exhibited an enhanced
activity of suppressing proliferation and migration of HCC cells when compared with free API-1. The mechanism study showed that API-LP upregulated miRNA biogenesis via inhibiting Pin1 activity followed by restoring the nucleus-to-cytoplasm export of XPO5. Because of the increased delivery efficiency, API-LP displayed a stronger ability to promote miRNA biogenesis than free API-1. Importantly, API-LP displayed higher systemic exposure than free API-1 in mice without apparent toxicity, resulting in an enhanced tumor inhibition in xenograft mice.
: The development and assessment of API-LP provide an attractive and safe anti-HCC agent, highlighting the miRNA-based treatment for human cancers. |
| doi_str_mv | 10.7150/thno.34588 |
| format | Article |
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bioavailability of API-1 limit its clinical application. To address these issues, we herein developed a liposomal formulation of API-1 to improve API-1 delivery and enhance its anti-HCC efficacy.
: We designed and developed a nanoscale liposomal formulation of API-1, named as API-LP. Subsequently, the mean diameter, polydispersity, zeta potential, encapsulation efficiency and thermal properties of the optimization API-LP were characterized. The enhanced anti-HCC activity and the molecular mechanism of API-LP were investigated both
and
. Finally, the safety and pharmacokinetic property of API-LP were evaluated systematically.
: API-LP had good formulation characteristics and exhibited an enhanced
activity of suppressing proliferation and migration of HCC cells when compared with free API-1. The mechanism study showed that API-LP upregulated miRNA biogenesis via inhibiting Pin1 activity followed by restoring the nucleus-to-cytoplasm export of XPO5. Because of the increased delivery efficiency, API-LP displayed a stronger ability to promote miRNA biogenesis than free API-1. Importantly, API-LP displayed higher systemic exposure than free API-1 in mice without apparent toxicity, resulting in an enhanced tumor inhibition in xenograft mice.
: The development and assessment of API-LP provide an attractive and safe anti-HCC agent, highlighting the miRNA-based treatment for human cancers.</description><identifier>ISSN: 1838-7640</identifier><identifier>EISSN: 1838-7640</identifier><identifier>DOI: 10.7150/thno.34588</identifier><identifier>PMID: 31367251</identifier><language>eng</language><publisher>Australia: Ivyspring International Publisher Pty Ltd</publisher><subject>Apoptosis ; Bioavailability ; Biosynthesis ; Cell cycle ; Cold ; Efficiency ; Flow cytometry ; Gene expression ; Kinases ; Lipids ; Liver cancer ; MicroRNAs ; Particle size ; Phosphorylation ; Research Paper</subject><ispartof>Theranostics, 2019-01, Vol.9 (16), p.4704-4716</ispartof><rights>2019. This work is published under https://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><rights>The author(s) 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c472t-c85091e38848f322c5d528e7e621bdbcd28481ac1fb63ac7c1798908f2c2d50f3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6643437/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6643437/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27915,27916,53782,53784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31367251$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sun, Dan</creatorcontrib><creatorcontrib>Tan, Shuangyan</creatorcontrib><creatorcontrib>Xiong, Yanli</creatorcontrib><creatorcontrib>Pu, Wenchen</creatorcontrib><creatorcontrib>Li, Jiao</creatorcontrib><creatorcontrib>Wei, Wei</creatorcontrib><creatorcontrib>Huang, Canhua</creatorcontrib><creatorcontrib>Wei, Yu-Quan</creatorcontrib><creatorcontrib>Peng, Yong</creatorcontrib><title>MicroRNA Biogenesis is Enhanced by Liposome-Encapsulated Pin1 Inhibitor in Hepatocellular Carcinoma</title><title>Theranostics</title><addtitle>Theranostics</addtitle><description>Hepatocellular carcinoma (HCC) is in an urgent need of new, effective therapies to reduce morbidity and mortality. We have previously demonstrated that peptidyl-prolyl cis/trans isomerase Pin1 is a potential target for HCC therapy, due to its pivotal role in HCC development through regulating miRNA biogenesis, and discovered the small molecule API-1 as a novel and specific Pin1 inhibitor. Despite its significant anti-HCC activity, the low water solubility and
bioavailability of API-1 limit its clinical application. To address these issues, we herein developed a liposomal formulation of API-1 to improve API-1 delivery and enhance its anti-HCC efficacy.
: We designed and developed a nanoscale liposomal formulation of API-1, named as API-LP. Subsequently, the mean diameter, polydispersity, zeta potential, encapsulation efficiency and thermal properties of the optimization API-LP were characterized. The enhanced anti-HCC activity and the molecular mechanism of API-LP were investigated both
and
. Finally, the safety and pharmacokinetic property of API-LP were evaluated systematically.
: API-LP had good formulation characteristics and exhibited an enhanced
activity of suppressing proliferation and migration of HCC cells when compared with free API-1. The mechanism study showed that API-LP upregulated miRNA biogenesis via inhibiting Pin1 activity followed by restoring the nucleus-to-cytoplasm export of XPO5. Because of the increased delivery efficiency, API-LP displayed a stronger ability to promote miRNA biogenesis than free API-1. Importantly, API-LP displayed higher systemic exposure than free API-1 in mice without apparent toxicity, resulting in an enhanced tumor inhibition in xenograft mice.
: The development and assessment of API-LP provide an attractive and safe anti-HCC agent, highlighting the miRNA-based treatment for human cancers.</description><subject>Apoptosis</subject><subject>Bioavailability</subject><subject>Biosynthesis</subject><subject>Cell cycle</subject><subject>Cold</subject><subject>Efficiency</subject><subject>Flow cytometry</subject><subject>Gene expression</subject><subject>Kinases</subject><subject>Lipids</subject><subject>Liver cancer</subject><subject>MicroRNAs</subject><subject>Particle size</subject><subject>Phosphorylation</subject><subject>Research Paper</subject><issn>1838-7640</issn><issn>1838-7640</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNpdkV1LwzAUhoMoKtMbf4AUvBGhmo-2SW-EOaYbzA9Er0OapltGm9SkFfbvzZyOaTiQA-_DyznnBeAMwWuKUnjTLYy9JknK2B44RoywmGYJ3N_pj8Cp90sYXgJxjvJDcEQQyShO0TGQj1o6-_o0jO60nSujvPZRqLFZCCNVGRWraKZb622j4rGRovV9LbogvGiDoqlZ6EJ31kXaRBPVis5KVdcBcdFIOKmNbcQJOKhE7dXpzz8A7_fjt9Eknj0_TEfDWSwTirtYshTmSBHGElYRjGVappgpqjKMirKQJQ4CEhJVRUaEpBLRnOWQVVjiMoUVGYDbjW_bF40qpTKdEzVvnW6EW3ErNP-rGL3gc_vJsywhCaHB4PLHwNmPXvmON9qv9xFG2d5zjDNKE0oDPAAX_9Cl7Z0J63Gc5gxTiGkeqKsNFW7svVPVdhgE-To-vo6Pf8cX4PPd8bfob1jkC1qmlno</recordid><startdate>20190101</startdate><enddate>20190101</enddate><creator>Sun, Dan</creator><creator>Tan, Shuangyan</creator><creator>Xiong, Yanli</creator><creator>Pu, Wenchen</creator><creator>Li, Jiao</creator><creator>Wei, Wei</creator><creator>Huang, Canhua</creator><creator>Wei, Yu-Quan</creator><creator>Peng, Yong</creator><general>Ivyspring International Publisher Pty Ltd</general><general>Ivyspring International Publisher</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20190101</creationdate><title>MicroRNA Biogenesis is Enhanced by Liposome-Encapsulated Pin1 Inhibitor in Hepatocellular Carcinoma</title><author>Sun, Dan ; Tan, Shuangyan ; Xiong, Yanli ; Pu, Wenchen ; Li, Jiao ; Wei, Wei ; Huang, Canhua ; Wei, Yu-Quan ; Peng, Yong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c472t-c85091e38848f322c5d528e7e621bdbcd28481ac1fb63ac7c1798908f2c2d50f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Apoptosis</topic><topic>Bioavailability</topic><topic>Biosynthesis</topic><topic>Cell cycle</topic><topic>Cold</topic><topic>Efficiency</topic><topic>Flow cytometry</topic><topic>Gene expression</topic><topic>Kinases</topic><topic>Lipids</topic><topic>Liver cancer</topic><topic>MicroRNAs</topic><topic>Particle size</topic><topic>Phosphorylation</topic><topic>Research Paper</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sun, Dan</creatorcontrib><creatorcontrib>Tan, Shuangyan</creatorcontrib><creatorcontrib>Xiong, Yanli</creatorcontrib><creatorcontrib>Pu, Wenchen</creatorcontrib><creatorcontrib>Li, Jiao</creatorcontrib><creatorcontrib>Wei, Wei</creatorcontrib><creatorcontrib>Huang, Canhua</creatorcontrib><creatorcontrib>Wei, Yu-Quan</creatorcontrib><creatorcontrib>Peng, Yong</creatorcontrib><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>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 Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</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 Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</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 China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Theranostics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sun, Dan</au><au>Tan, Shuangyan</au><au>Xiong, Yanli</au><au>Pu, Wenchen</au><au>Li, Jiao</au><au>Wei, Wei</au><au>Huang, Canhua</au><au>Wei, Yu-Quan</au><au>Peng, Yong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MicroRNA Biogenesis is Enhanced by Liposome-Encapsulated Pin1 Inhibitor in Hepatocellular Carcinoma</atitle><jtitle>Theranostics</jtitle><addtitle>Theranostics</addtitle><date>2019-01-01</date><risdate>2019</risdate><volume>9</volume><issue>16</issue><spage>4704</spage><epage>4716</epage><pages>4704-4716</pages><issn>1838-7640</issn><eissn>1838-7640</eissn><abstract>Hepatocellular carcinoma (HCC) is in an urgent need of new, effective therapies to reduce morbidity and mortality. We have previously demonstrated that peptidyl-prolyl cis/trans isomerase Pin1 is a potential target for HCC therapy, due to its pivotal role in HCC development through regulating miRNA biogenesis, and discovered the small molecule API-1 as a novel and specific Pin1 inhibitor. Despite its significant anti-HCC activity, the low water solubility and
bioavailability of API-1 limit its clinical application. To address these issues, we herein developed a liposomal formulation of API-1 to improve API-1 delivery and enhance its anti-HCC efficacy.
: We designed and developed a nanoscale liposomal formulation of API-1, named as API-LP. Subsequently, the mean diameter, polydispersity, zeta potential, encapsulation efficiency and thermal properties of the optimization API-LP were characterized. The enhanced anti-HCC activity and the molecular mechanism of API-LP were investigated both
and
. Finally, the safety and pharmacokinetic property of API-LP were evaluated systematically.
: API-LP had good formulation characteristics and exhibited an enhanced
activity of suppressing proliferation and migration of HCC cells when compared with free API-1. The mechanism study showed that API-LP upregulated miRNA biogenesis via inhibiting Pin1 activity followed by restoring the nucleus-to-cytoplasm export of XPO5. Because of the increased delivery efficiency, API-LP displayed a stronger ability to promote miRNA biogenesis than free API-1. Importantly, API-LP displayed higher systemic exposure than free API-1 in mice without apparent toxicity, resulting in an enhanced tumor inhibition in xenograft mice.
: The development and assessment of API-LP provide an attractive and safe anti-HCC agent, highlighting the miRNA-based treatment for human cancers.</abstract><cop>Australia</cop><pub>Ivyspring International Publisher Pty Ltd</pub><pmid>31367251</pmid><doi>10.7150/thno.34588</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Apoptosis Bioavailability Biosynthesis Cell cycle Cold Efficiency Flow cytometry Gene expression Kinases Lipids Liver cancer MicroRNAs Particle size Phosphorylation Research Paper |
| title | MicroRNA Biogenesis is Enhanced by Liposome-Encapsulated Pin1 Inhibitor in Hepatocellular Carcinoma |
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