Self-assembled amphiphile-based nanoparticles for the inhibition of hepatocellular carcinoma metastasis via ICAM-1 mediated cell adhesion
Nanosized drug delivery systems have emerged to improve the therapeutic performance of anticancer drugs. Here, an amphiphile-based nanoparticle consisting of amphiphilic prodrug N-[3b-acetoxy-urs-12-en-28-oyl]-amino-2-methylpiperazine was developed (UP12 NPs) with uniform sizes (~100 nm), which poss...
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| Veröffentlicht in: | Acta biomaterialia 2020-07, Vol.111, p.373-385 |
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| creator | Zhao, Rui-Rui Fang, Yi-Fan Chen, Zi-Xuan Le, Jing-Qing Jiang, Long-Guang Shao, Jing-Wei |
| description | Nanosized drug delivery systems have emerged to improve the therapeutic performance of anticancer drugs. Here, an amphiphile-based nanoparticle consisting of amphiphilic prodrug N-[3b-acetoxy-urs-12-en-28-oyl]-amino-2-methylpiperazine was developed (UP12 NPs) with uniform sizes (~100 nm), which possessed the advantages of small molecules and nanomedicine. The positively charged UP12 NPs significantly enhanced the cellular drug uptake on HepG2 cells than negatively charged UA NPs. Meanwhile, UP12 and these therapeutic amphiphile-based nanoparticles could induce cell apoptosis more efficiently than that of UA and UA NPs. Moreover, molecular docking demonstrated that the UP12 and intercellular adhesion molecule 1 (ICAM-1) could dock well. UP12 and UP12 NPs significantly decreased the mRNA expression of ICAM-1 and inhibited the migration and adhesion of liver cancer cells (HepG2 cells), which indicated that UP12 might be one of the potential ICAM-1 inhibitors. In vivo, UP12 NPs enhanced tumor accumulation, inhibited tumor lung metastasis and showed good biocompatibility. Overall, UP12 or UP12 NPs could be developed as prospective drugs for cancer metastasis therapy via ICAM-1 mediated cell adhesion.
In this study, we fabricated the therapeutic amphiphile-based nanoparticles by assembly of ursolic acid piperazine derivative N-[3b-acetoxy-urs-12-en-28-oyl]-amino-2-methylpiperazine (name as UP12 NPs) with low cytotoxicity. UP12 NPs exhibited spherical morphology and uniform sizes. Particularly, these therapeutic amphiphile-based nanoparticles significantly enhanced tumor accumulation and inhibited tumor lung metastases via intercellular adhesion molecule 1 (ICAM-1) mediated cell adhesion.
[Display omitted] |
| doi_str_mv | 10.1016/j.actbio.2020.04.050 |
| format | Article |
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In this study, we fabricated the therapeutic amphiphile-based nanoparticles by assembly of ursolic acid piperazine derivative N-[3b-acetoxy-urs-12-en-28-oyl]-amino-2-methylpiperazine (name as UP12 NPs) with low cytotoxicity. UP12 NPs exhibited spherical morphology and uniform sizes. Particularly, these therapeutic amphiphile-based nanoparticles significantly enhanced tumor accumulation and inhibited tumor lung metastases via intercellular adhesion molecule 1 (ICAM-1) mediated cell adhesion.
[Display omitted]</description><identifier>ISSN: 1742-7061</identifier><identifier>EISSN: 1878-7568</identifier><identifier>DOI: 10.1016/j.actbio.2020.04.050</identifier><identifier>PMID: 32413580</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adhesion ; Antineoplastic drugs ; Antitumor agents ; Apoptosis ; Biocompatibility ; Cancer Metastasis ; Carcinoma, Hepatocellular - drug therapy ; Cell Adhesion ; Cell adhesion & migration ; Cell Line, Tumor ; Drug delivery ; Drug Delivery Systems ; Gene expression ; Hepatocellular carcinoma ; Hepatocytes ; Humans ; ICAM-1 ; Intercellular Adhesion Molecule-1 ; Liver cancer ; Liver Neoplasms - drug therapy ; Metastases ; Metastasis ; Molecular docking ; Molecular Docking Simulation ; Nanoparticles ; Nanotechnology ; Prospective Studies ; Self-assembly ; Therapeutic amphiphile-based nanoparticles ; Tumors ; Ursolic acid derivative</subject><ispartof>Acta biomaterialia, 2020-07, Vol.111, p.373-385</ispartof><rights>2020 Acta Materialia Inc.</rights><rights>Copyright © 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier BV Jul 2020</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c390t-4b558e5382f6e1aae2f911e7f1876b16fca2c500dd9277707a6846b8399de36d3</citedby><cites>FETCH-LOGICAL-c390t-4b558e5382f6e1aae2f911e7f1876b16fca2c500dd9277707a6846b8399de36d3</cites><orcidid>0000-0002-2060-8887 ; 0000-0002-7937-3795</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.actbio.2020.04.050$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32413580$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhao, Rui-Rui</creatorcontrib><creatorcontrib>Fang, Yi-Fan</creatorcontrib><creatorcontrib>Chen, Zi-Xuan</creatorcontrib><creatorcontrib>Le, Jing-Qing</creatorcontrib><creatorcontrib>Jiang, Long-Guang</creatorcontrib><creatorcontrib>Shao, Jing-Wei</creatorcontrib><title>Self-assembled amphiphile-based nanoparticles for the inhibition of hepatocellular carcinoma metastasis via ICAM-1 mediated cell adhesion</title><title>Acta biomaterialia</title><addtitle>Acta Biomater</addtitle><description>Nanosized drug delivery systems have emerged to improve the therapeutic performance of anticancer drugs. Here, an amphiphile-based nanoparticle consisting of amphiphilic prodrug N-[3b-acetoxy-urs-12-en-28-oyl]-amino-2-methylpiperazine was developed (UP12 NPs) with uniform sizes (~100 nm), which possessed the advantages of small molecules and nanomedicine. The positively charged UP12 NPs significantly enhanced the cellular drug uptake on HepG2 cells than negatively charged UA NPs. Meanwhile, UP12 and these therapeutic amphiphile-based nanoparticles could induce cell apoptosis more efficiently than that of UA and UA NPs. Moreover, molecular docking demonstrated that the UP12 and intercellular adhesion molecule 1 (ICAM-1) could dock well. UP12 and UP12 NPs significantly decreased the mRNA expression of ICAM-1 and inhibited the migration and adhesion of liver cancer cells (HepG2 cells), which indicated that UP12 might be one of the potential ICAM-1 inhibitors. In vivo, UP12 NPs enhanced tumor accumulation, inhibited tumor lung metastasis and showed good biocompatibility. Overall, UP12 or UP12 NPs could be developed as prospective drugs for cancer metastasis therapy via ICAM-1 mediated cell adhesion.
In this study, we fabricated the therapeutic amphiphile-based nanoparticles by assembly of ursolic acid piperazine derivative N-[3b-acetoxy-urs-12-en-28-oyl]-amino-2-methylpiperazine (name as UP12 NPs) with low cytotoxicity. UP12 NPs exhibited spherical morphology and uniform sizes. Particularly, these therapeutic amphiphile-based nanoparticles significantly enhanced tumor accumulation and inhibited tumor lung metastases via intercellular adhesion molecule 1 (ICAM-1) mediated cell adhesion.
[Display omitted]</description><subject>Adhesion</subject><subject>Antineoplastic drugs</subject><subject>Antitumor agents</subject><subject>Apoptosis</subject><subject>Biocompatibility</subject><subject>Cancer Metastasis</subject><subject>Carcinoma, Hepatocellular - drug therapy</subject><subject>Cell Adhesion</subject><subject>Cell adhesion & migration</subject><subject>Cell Line, Tumor</subject><subject>Drug delivery</subject><subject>Drug Delivery Systems</subject><subject>Gene expression</subject><subject>Hepatocellular carcinoma</subject><subject>Hepatocytes</subject><subject>Humans</subject><subject>ICAM-1</subject><subject>Intercellular Adhesion Molecule-1</subject><subject>Liver cancer</subject><subject>Liver Neoplasms - drug therapy</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Molecular docking</subject><subject>Molecular Docking Simulation</subject><subject>Nanoparticles</subject><subject>Nanotechnology</subject><subject>Prospective Studies</subject><subject>Self-assembly</subject><subject>Therapeutic amphiphile-based nanoparticles</subject><subject>Tumors</subject><subject>Ursolic acid derivative</subject><issn>1742-7061</issn><issn>1878-7568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcGK1TAUhosozjj6BiIBN256TdI0STeCDOoIIy7UdThNT2kubVOTdMBH8K09lzu6cDEkkHD4_j8n56-ql4IfBBf67fEAvvQhHiSX_MDVgbf8UXUprLG1abV9THejZG24FhfVs5yPnDdWSPu0umikEk1r-WX1-xvOYw0549LPODBYtinQnrHuIVNhhTVukErwM2Y2xsTKhCysU-hDCXFlcWQTblCix3neZ0jMQ_JhjQuwBQtk2iGzuwDs8_X7L7Wg6hCgkPdJwWCYMJPR8-rJCHPGF_fnVfXj44fv1zf17ddPJLytfdPxUqu-bS22jZWjRgGAcuyEQDPSx3Uv9OhB-pbzYeikMYYb0Fbp3jZdN2Cjh-aqenP23VL8uWMubgn51AmsGPfspOK0tGgNoa__Q49xTyt1R5SidmzXKqLUmfIp5pxwdFsKC6RfTnB3isod3Tkqd4rKceUoKpK9ujffe5rIP9HfbAh4dwaQpnEXMLnsA66eppfQFzfE8PALfwCJAqew</recordid><startdate>20200715</startdate><enddate>20200715</enddate><creator>Zhao, Rui-Rui</creator><creator>Fang, Yi-Fan</creator><creator>Chen, Zi-Xuan</creator><creator>Le, Jing-Qing</creator><creator>Jiang, Long-Guang</creator><creator>Shao, Jing-Wei</creator><general>Elsevier Ltd</general><general>Elsevier BV</general><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>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-2060-8887</orcidid><orcidid>https://orcid.org/0000-0002-7937-3795</orcidid></search><sort><creationdate>20200715</creationdate><title>Self-assembled amphiphile-based nanoparticles for the inhibition of hepatocellular carcinoma metastasis via ICAM-1 mediated cell adhesion</title><author>Zhao, Rui-Rui ; 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Here, an amphiphile-based nanoparticle consisting of amphiphilic prodrug N-[3b-acetoxy-urs-12-en-28-oyl]-amino-2-methylpiperazine was developed (UP12 NPs) with uniform sizes (~100 nm), which possessed the advantages of small molecules and nanomedicine. The positively charged UP12 NPs significantly enhanced the cellular drug uptake on HepG2 cells than negatively charged UA NPs. Meanwhile, UP12 and these therapeutic amphiphile-based nanoparticles could induce cell apoptosis more efficiently than that of UA and UA NPs. Moreover, molecular docking demonstrated that the UP12 and intercellular adhesion molecule 1 (ICAM-1) could dock well. UP12 and UP12 NPs significantly decreased the mRNA expression of ICAM-1 and inhibited the migration and adhesion of liver cancer cells (HepG2 cells), which indicated that UP12 might be one of the potential ICAM-1 inhibitors. In vivo, UP12 NPs enhanced tumor accumulation, inhibited tumor lung metastasis and showed good biocompatibility. Overall, UP12 or UP12 NPs could be developed as prospective drugs for cancer metastasis therapy via ICAM-1 mediated cell adhesion.
In this study, we fabricated the therapeutic amphiphile-based nanoparticles by assembly of ursolic acid piperazine derivative N-[3b-acetoxy-urs-12-en-28-oyl]-amino-2-methylpiperazine (name as UP12 NPs) with low cytotoxicity. UP12 NPs exhibited spherical morphology and uniform sizes. Particularly, these therapeutic amphiphile-based nanoparticles significantly enhanced tumor accumulation and inhibited tumor lung metastases via intercellular adhesion molecule 1 (ICAM-1) mediated cell adhesion.
[Display omitted]</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>32413580</pmid><doi>10.1016/j.actbio.2020.04.050</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-2060-8887</orcidid><orcidid>https://orcid.org/0000-0002-7937-3795</orcidid></addata></record> |
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| subjects | Adhesion Antineoplastic drugs Antitumor agents Apoptosis Biocompatibility Cancer Metastasis Carcinoma, Hepatocellular - drug therapy Cell Adhesion Cell adhesion & migration Cell Line, Tumor Drug delivery Drug Delivery Systems Gene expression Hepatocellular carcinoma Hepatocytes Humans ICAM-1 Intercellular Adhesion Molecule-1 Liver cancer Liver Neoplasms - drug therapy Metastases Metastasis Molecular docking Molecular Docking Simulation Nanoparticles Nanotechnology Prospective Studies Self-assembly Therapeutic amphiphile-based nanoparticles Tumors Ursolic acid derivative |
| title | Self-assembled amphiphile-based nanoparticles for the inhibition of hepatocellular carcinoma metastasis via ICAM-1 mediated cell adhesion |
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