Niclosamide-loaded polymeric micelles ameliorate hepatocellular carcinoma in vivo through targeting Wnt and Notch pathways
Niclosamide (NIC) is an anthelmintic agent repurposed as a potent anticancer agent. However, its use is hindered by its poor solubility. We investigated the underlying mechanisms of NIC anticancer activity employing a novel oral NIC pluronic-based nanoformulation and tested its effect in thioacetami...
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| Veröffentlicht in: | Life sciences (1973) 2020-11, Vol.261, p.118458, Article 118458 |
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| creator | Zeyada, Menna S. Abdel-Rahman, Noha El-Karef, Amro Yahia, Sarah El-Sherbiny, Ibrahim M. Eissa, Laila A. |
| description | Niclosamide (NIC) is an anthelmintic agent repurposed as a potent anticancer agent. However, its use is hindered by its poor solubility. We investigated the underlying mechanisms of NIC anticancer activity employing a novel oral NIC pluronic-based nanoformulation and tested its effect in thioacetamide-induced hepatocellular carcinoma (HCC) in rats. We evaluated its antitumor effect through regulating Wnt/β-catenin and Notch signaling pathways and apoptosis.
Niclosamide-loaded pluronic nanoparticles (NIC-NPs) were optimally developed and characterized with sustained release properties up to 7 days. Sixteen weeks after HCC induction, NIC (70 mg/kg) and an equivalent dose of NIC-NPs were administered orally for 3 consecutive weeks. Hepatocyte integrity was assessed by measuring serum levels of aminotransferases, ALP, GGT, bilirubin, albumin and total protein. HCC development was detected by measuring AFP expression. Necroinflammation and fibrosis were scored by histopathological examination. Wnt/β-catenin and Notch signaling were evaluated by measuring hepatic mRNA levels of Wnt3A, Lrp5 and Lrp6 Co-receptors, Dvl-2, Notch1 and Hes1 and β-catenin protein levels. Apoptosis was assessed by measuring mRNA and protein levels of cyclin D1 and caspase-3.
The novel NIC-NPs restored liver integrity, reduced AFP levels and showed improved anticancer and proapoptotic activities compared to drug alone. The inhibitory effect of NIC on Wnt/β-catenin and Notch signaling pathways was potentiated by the NIC-NPs formulation.
We conclude that NIC acts by inhibiting Wnt/β-catenin and Notch signaling and inducing apoptosis in HCC. Developing pluronic-based nanoformulations may be a promising approach to improve NIC solubility and offer the possibility of controlled release.
•Thioacetamide induced aberrant Wingless and Notch activation in liver.•Niclosamide ameliorates hepatocellular carcinoma by inhibition of Wingless and Notch pathways.•Niclosamide-loaded pluronic nanoparticles potentiated niclosamide inhibitory effect.•Niclosamide-loaded pluronic nanoparticles ameliorated niclosamide efficacy.•Niclosamide nanoparticles could be considered a promising approach for targeting hepatocellular carcinoma. |
| doi_str_mv | 10.1016/j.lfs.2020.118458 |
| format | Article |
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Niclosamide-loaded pluronic nanoparticles (NIC-NPs) were optimally developed and characterized with sustained release properties up to 7 days. Sixteen weeks after HCC induction, NIC (70 mg/kg) and an equivalent dose of NIC-NPs were administered orally for 3 consecutive weeks. Hepatocyte integrity was assessed by measuring serum levels of aminotransferases, ALP, GGT, bilirubin, albumin and total protein. HCC development was detected by measuring AFP expression. Necroinflammation and fibrosis were scored by histopathological examination. Wnt/β-catenin and Notch signaling were evaluated by measuring hepatic mRNA levels of Wnt3A, Lrp5 and Lrp6 Co-receptors, Dvl-2, Notch1 and Hes1 and β-catenin protein levels. Apoptosis was assessed by measuring mRNA and protein levels of cyclin D1 and caspase-3.
The novel NIC-NPs restored liver integrity, reduced AFP levels and showed improved anticancer and proapoptotic activities compared to drug alone. The inhibitory effect of NIC on Wnt/β-catenin and Notch signaling pathways was potentiated by the NIC-NPs formulation.
We conclude that NIC acts by inhibiting Wnt/β-catenin and Notch signaling and inducing apoptosis in HCC. Developing pluronic-based nanoformulations may be a promising approach to improve NIC solubility and offer the possibility of controlled release.
•Thioacetamide induced aberrant Wingless and Notch activation in liver.•Niclosamide ameliorates hepatocellular carcinoma by inhibition of Wingless and Notch pathways.•Niclosamide-loaded pluronic nanoparticles potentiated niclosamide inhibitory effect.•Niclosamide-loaded pluronic nanoparticles ameliorated niclosamide efficacy.•Niclosamide nanoparticles could be considered a promising approach for targeting hepatocellular carcinoma.</description><identifier>ISSN: 0024-3205</identifier><identifier>EISSN: 1879-0631</identifier><identifier>DOI: 10.1016/j.lfs.2020.118458</identifier><identifier>PMID: 32961231</identifier><language>eng</language><publisher>OXFORD: Elsevier Inc</publisher><subject><![CDATA[Albumins ; Animals ; Anthelmintic agents ; Anthelmintics - administration & dosage ; Anthelmintics - therapeutic use ; Anticancer properties ; Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - therapeutic use ; Antiparasitic agents ; Antitumor activity ; Apoptosis ; Bilirubin ; Carcinoma, Hepatocellular - drug therapy ; Carcinoma, Hepatocellular - metabolism ; Carcinoma, Hepatocellular - pathology ; Caspase-3 ; Controlled release ; Cyclin D1 ; Dishevelled protein ; Drug Carriers - chemistry ; Evaluation ; Fibrosis ; Hepatocellular carcinoma ; Integrity ; Life Sciences & Biomedicine ; Liver cancer ; Liver Neoplasms - drug therapy ; Liver Neoplasms - metabolism ; Liver Neoplasms - pathology ; LRP5 protein ; Male ; Medicine, Research & Experimental ; Micelles ; mRNA ; Nanoparticles ; Nanoparticles - chemistry ; Niclosamide ; Niclosamide - administration & dosage ; Niclosamide - therapeutic use ; Niclosamide-pluronic nanoparticles ; Notch ; Notch1 protein ; Oral administration ; Pharmacology & Pharmacy ; Proteins ; Rats, Sprague-Dawley ; Receptors, Notch - metabolism ; Research & Experimental Medicine ; Science & Technology ; Serum levels ; Signal transduction ; Signal Transduction - drug effects ; Signaling ; Solubility ; Sustained release ; Thioacetamide ; Wingless/β-catenin ; Wnt protein ; Wnt Signaling Pathway - drug effects ; β-Catenin]]></subject><ispartof>Life sciences (1973), 2020-11, Vol.261, p.118458, Article 118458</ispartof><rights>2020</rights><rights>Copyright © 2020. Published by Elsevier Inc.</rights><rights>Copyright Elsevier BV Nov 15, 2020</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>22</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000588290900050</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c381t-b20690bfc33d6ba839dff4ea713ff2bc9e549f72e07f7b5c7da3b3a2926b90c63</citedby><cites>FETCH-LOGICAL-c381t-b20690bfc33d6ba839dff4ea713ff2bc9e549f72e07f7b5c7da3b3a2926b90c63</cites><orcidid>0000-0002-8179-437X ; 0000-0003-4470-0263</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.lfs.2020.118458$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,782,786,3554,27933,27934,28257,46004</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32961231$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zeyada, Menna S.</creatorcontrib><creatorcontrib>Abdel-Rahman, Noha</creatorcontrib><creatorcontrib>El-Karef, Amro</creatorcontrib><creatorcontrib>Yahia, Sarah</creatorcontrib><creatorcontrib>El-Sherbiny, Ibrahim M.</creatorcontrib><creatorcontrib>Eissa, Laila A.</creatorcontrib><title>Niclosamide-loaded polymeric micelles ameliorate hepatocellular carcinoma in vivo through targeting Wnt and Notch pathways</title><title>Life sciences (1973)</title><addtitle>LIFE SCI</addtitle><addtitle>Life Sci</addtitle><description>Niclosamide (NIC) is an anthelmintic agent repurposed as a potent anticancer agent. However, its use is hindered by its poor solubility. We investigated the underlying mechanisms of NIC anticancer activity employing a novel oral NIC pluronic-based nanoformulation and tested its effect in thioacetamide-induced hepatocellular carcinoma (HCC) in rats. We evaluated its antitumor effect through regulating Wnt/β-catenin and Notch signaling pathways and apoptosis.
Niclosamide-loaded pluronic nanoparticles (NIC-NPs) were optimally developed and characterized with sustained release properties up to 7 days. Sixteen weeks after HCC induction, NIC (70 mg/kg) and an equivalent dose of NIC-NPs were administered orally for 3 consecutive weeks. Hepatocyte integrity was assessed by measuring serum levels of aminotransferases, ALP, GGT, bilirubin, albumin and total protein. HCC development was detected by measuring AFP expression. Necroinflammation and fibrosis were scored by histopathological examination. Wnt/β-catenin and Notch signaling were evaluated by measuring hepatic mRNA levels of Wnt3A, Lrp5 and Lrp6 Co-receptors, Dvl-2, Notch1 and Hes1 and β-catenin protein levels. Apoptosis was assessed by measuring mRNA and protein levels of cyclin D1 and caspase-3.
The novel NIC-NPs restored liver integrity, reduced AFP levels and showed improved anticancer and proapoptotic activities compared to drug alone. The inhibitory effect of NIC on Wnt/β-catenin and Notch signaling pathways was potentiated by the NIC-NPs formulation.
We conclude that NIC acts by inhibiting Wnt/β-catenin and Notch signaling and inducing apoptosis in HCC. Developing pluronic-based nanoformulations may be a promising approach to improve NIC solubility and offer the possibility of controlled release.
•Thioacetamide induced aberrant Wingless and Notch activation in liver.•Niclosamide ameliorates hepatocellular carcinoma by inhibition of Wingless and Notch pathways.•Niclosamide-loaded pluronic nanoparticles potentiated niclosamide inhibitory effect.•Niclosamide-loaded pluronic nanoparticles ameliorated niclosamide efficacy.•Niclosamide nanoparticles could be considered a promising approach for targeting hepatocellular carcinoma.</description><subject>Albumins</subject><subject>Animals</subject><subject>Anthelmintic agents</subject><subject>Anthelmintics - administration & dosage</subject><subject>Anthelmintics - therapeutic use</subject><subject>Anticancer properties</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Antiparasitic agents</subject><subject>Antitumor activity</subject><subject>Apoptosis</subject><subject>Bilirubin</subject><subject>Carcinoma, Hepatocellular - drug therapy</subject><subject>Carcinoma, Hepatocellular - metabolism</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Caspase-3</subject><subject>Controlled release</subject><subject>Cyclin D1</subject><subject>Dishevelled protein</subject><subject>Drug Carriers - chemistry</subject><subject>Evaluation</subject><subject>Fibrosis</subject><subject>Hepatocellular carcinoma</subject><subject>Integrity</subject><subject>Life Sciences & Biomedicine</subject><subject>Liver cancer</subject><subject>Liver Neoplasms - drug therapy</subject><subject>Liver Neoplasms - metabolism</subject><subject>Liver Neoplasms - pathology</subject><subject>LRP5 protein</subject><subject>Male</subject><subject>Medicine, Research & Experimental</subject><subject>Micelles</subject><subject>mRNA</subject><subject>Nanoparticles</subject><subject>Nanoparticles - chemistry</subject><subject>Niclosamide</subject><subject>Niclosamide - administration & dosage</subject><subject>Niclosamide - therapeutic use</subject><subject>Niclosamide-pluronic nanoparticles</subject><subject>Notch</subject><subject>Notch1 protein</subject><subject>Oral administration</subject><subject>Pharmacology & Pharmacy</subject><subject>Proteins</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, Notch - metabolism</subject><subject>Research & Experimental Medicine</subject><subject>Science & Technology</subject><subject>Serum levels</subject><subject>Signal transduction</subject><subject>Signal Transduction - drug effects</subject><subject>Signaling</subject><subject>Solubility</subject><subject>Sustained release</subject><subject>Thioacetamide</subject><subject>Wingless/β-catenin</subject><subject>Wnt protein</subject><subject>Wnt Signaling Pathway - drug effects</subject><subject>β-Catenin</subject><issn>0024-3205</issn><issn>1879-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>AOWDO</sourceid><sourceid>EIF</sourceid><recordid>eNqNkU2L1DAYgIMo7rj6A7xIwKN0zEe_gicZVldY1oviMaTJm2mGthmTdJbx15vS2T2Kp3zwPAl5gtBbSraU0PrjYTvYuGWE5TVty6p9hja0bURBak6fow0hrCw4I9UVehXjgRBSVQ1_ia44EzVlnG7Qn3unBx_V6AwUg1cGDD764TxCcBqPTsMwQMRqhMH5oBLgHo4q-WV_HlTAWgXtJj8q7CZ8ciePUx_8vO9xUmEPyU17_GtKWE0G3_uke5z1_kGd42v0wqohwpvLeI1-frn5sbst7r5__bb7fFdo3tJUdIzUgnRWc27qTrVcGGtLUA3l1rJOC6hKYRsGpLFNV-nGKN5xxQSrO0F0za_R-_XcY_C_Z4hJHvwcpnylZBWp67IhrM0UXSkdfIwBrDwGN6pwlpTIpbY8yFxbLrXlWjs77y4nz90I5sl4zJuBDyvwAJ23UTuYNDxhy3-0LRNELDOS6fb_6Z1LKjk_7fw8pax-WlXIIU8OgrzoxgXQSRrv_vGOv_4rs1w</recordid><startdate>20201115</startdate><enddate>20201115</enddate><creator>Zeyada, Menna S.</creator><creator>Abdel-Rahman, Noha</creator><creator>El-Karef, Amro</creator><creator>Yahia, Sarah</creator><creator>El-Sherbiny, Ibrahim M.</creator><creator>Eissa, Laila A.</creator><general>Elsevier Inc</general><general>Elsevier</general><general>Elsevier BV</general><scope>AOWDO</scope><scope>BLEPL</scope><scope>DTL</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>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><orcidid>https://orcid.org/0000-0002-8179-437X</orcidid><orcidid>https://orcid.org/0000-0003-4470-0263</orcidid></search><sort><creationdate>20201115</creationdate><title>Niclosamide-loaded polymeric micelles ameliorate hepatocellular carcinoma in vivo through targeting Wnt and Notch pathways</title><author>Zeyada, Menna S. ; Abdel-Rahman, Noha ; El-Karef, Amro ; Yahia, Sarah ; El-Sherbiny, Ibrahim M. ; Eissa, Laila A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c381t-b20690bfc33d6ba839dff4ea713ff2bc9e549f72e07f7b5c7da3b3a2926b90c63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Albumins</topic><topic>Animals</topic><topic>Anthelmintic agents</topic><topic>Anthelmintics - administration & dosage</topic><topic>Anthelmintics - therapeutic use</topic><topic>Anticancer properties</topic><topic>Antineoplastic Agents - administration & dosage</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Antiparasitic agents</topic><topic>Antitumor activity</topic><topic>Apoptosis</topic><topic>Bilirubin</topic><topic>Carcinoma, Hepatocellular - drug therapy</topic><topic>Carcinoma, Hepatocellular - metabolism</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Caspase-3</topic><topic>Controlled release</topic><topic>Cyclin D1</topic><topic>Dishevelled protein</topic><topic>Drug Carriers - chemistry</topic><topic>Evaluation</topic><topic>Fibrosis</topic><topic>Hepatocellular carcinoma</topic><topic>Integrity</topic><topic>Life Sciences & Biomedicine</topic><topic>Liver cancer</topic><topic>Liver Neoplasms - drug therapy</topic><topic>Liver Neoplasms - metabolism</topic><topic>Liver Neoplasms - pathology</topic><topic>LRP5 protein</topic><topic>Male</topic><topic>Medicine, Research & Experimental</topic><topic>Micelles</topic><topic>mRNA</topic><topic>Nanoparticles</topic><topic>Nanoparticles - chemistry</topic><topic>Niclosamide</topic><topic>Niclosamide - administration & dosage</topic><topic>Niclosamide - therapeutic use</topic><topic>Niclosamide-pluronic nanoparticles</topic><topic>Notch</topic><topic>Notch1 protein</topic><topic>Oral administration</topic><topic>Pharmacology & Pharmacy</topic><topic>Proteins</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, Notch - metabolism</topic><topic>Research & Experimental Medicine</topic><topic>Science & Technology</topic><topic>Serum levels</topic><topic>Signal transduction</topic><topic>Signal Transduction - drug effects</topic><topic>Signaling</topic><topic>Solubility</topic><topic>Sustained release</topic><topic>Thioacetamide</topic><topic>Wingless/β-catenin</topic><topic>Wnt protein</topic><topic>Wnt Signaling Pathway - drug effects</topic><topic>β-Catenin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zeyada, Menna S.</creatorcontrib><creatorcontrib>Abdel-Rahman, Noha</creatorcontrib><creatorcontrib>El-Karef, Amro</creatorcontrib><creatorcontrib>Yahia, Sarah</creatorcontrib><creatorcontrib>El-Sherbiny, Ibrahim M.</creatorcontrib><creatorcontrib>Eissa, Laila A.</creatorcontrib><collection>Web of Science - Science Citation Index Expanded - 2020</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Life sciences (1973)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zeyada, Menna S.</au><au>Abdel-Rahman, Noha</au><au>El-Karef, Amro</au><au>Yahia, Sarah</au><au>El-Sherbiny, Ibrahim M.</au><au>Eissa, Laila A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Niclosamide-loaded polymeric micelles ameliorate hepatocellular carcinoma in vivo through targeting Wnt and Notch pathways</atitle><jtitle>Life sciences (1973)</jtitle><stitle>LIFE SCI</stitle><addtitle>Life Sci</addtitle><date>2020-11-15</date><risdate>2020</risdate><volume>261</volume><spage>118458</spage><pages>118458-</pages><artnum>118458</artnum><issn>0024-3205</issn><eissn>1879-0631</eissn><abstract>Niclosamide (NIC) is an anthelmintic agent repurposed as a potent anticancer agent. However, its use is hindered by its poor solubility. We investigated the underlying mechanisms of NIC anticancer activity employing a novel oral NIC pluronic-based nanoformulation and tested its effect in thioacetamide-induced hepatocellular carcinoma (HCC) in rats. We evaluated its antitumor effect through regulating Wnt/β-catenin and Notch signaling pathways and apoptosis.
Niclosamide-loaded pluronic nanoparticles (NIC-NPs) were optimally developed and characterized with sustained release properties up to 7 days. Sixteen weeks after HCC induction, NIC (70 mg/kg) and an equivalent dose of NIC-NPs were administered orally for 3 consecutive weeks. Hepatocyte integrity was assessed by measuring serum levels of aminotransferases, ALP, GGT, bilirubin, albumin and total protein. HCC development was detected by measuring AFP expression. Necroinflammation and fibrosis were scored by histopathological examination. Wnt/β-catenin and Notch signaling were evaluated by measuring hepatic mRNA levels of Wnt3A, Lrp5 and Lrp6 Co-receptors, Dvl-2, Notch1 and Hes1 and β-catenin protein levels. Apoptosis was assessed by measuring mRNA and protein levels of cyclin D1 and caspase-3.
The novel NIC-NPs restored liver integrity, reduced AFP levels and showed improved anticancer and proapoptotic activities compared to drug alone. The inhibitory effect of NIC on Wnt/β-catenin and Notch signaling pathways was potentiated by the NIC-NPs formulation.
We conclude that NIC acts by inhibiting Wnt/β-catenin and Notch signaling and inducing apoptosis in HCC. Developing pluronic-based nanoformulations may be a promising approach to improve NIC solubility and offer the possibility of controlled release.
•Thioacetamide induced aberrant Wingless and Notch activation in liver.•Niclosamide ameliorates hepatocellular carcinoma by inhibition of Wingless and Notch pathways.•Niclosamide-loaded pluronic nanoparticles potentiated niclosamide inhibitory effect.•Niclosamide-loaded pluronic nanoparticles ameliorated niclosamide efficacy.•Niclosamide nanoparticles could be considered a promising approach for targeting hepatocellular carcinoma.</abstract><cop>OXFORD</cop><pub>Elsevier Inc</pub><pmid>32961231</pmid><doi>10.1016/j.lfs.2020.118458</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-8179-437X</orcidid><orcidid>https://orcid.org/0000-0003-4470-0263</orcidid></addata></record> |
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| subjects | Albumins Animals Anthelmintic agents Anthelmintics - administration & dosage Anthelmintics - therapeutic use Anticancer properties Antineoplastic Agents - administration & dosage Antineoplastic Agents - therapeutic use Antiparasitic agents Antitumor activity Apoptosis Bilirubin Carcinoma, Hepatocellular - drug therapy Carcinoma, Hepatocellular - metabolism Carcinoma, Hepatocellular - pathology Caspase-3 Controlled release Cyclin D1 Dishevelled protein Drug Carriers - chemistry Evaluation Fibrosis Hepatocellular carcinoma Integrity Life Sciences & Biomedicine Liver cancer Liver Neoplasms - drug therapy Liver Neoplasms - metabolism Liver Neoplasms - pathology LRP5 protein Male Medicine, Research & Experimental Micelles mRNA Nanoparticles Nanoparticles - chemistry Niclosamide Niclosamide - administration & dosage Niclosamide - therapeutic use Niclosamide-pluronic nanoparticles Notch Notch1 protein Oral administration Pharmacology & Pharmacy Proteins Rats, Sprague-Dawley Receptors, Notch - metabolism Research & Experimental Medicine Science & Technology Serum levels Signal transduction Signal Transduction - drug effects Signaling Solubility Sustained release Thioacetamide Wingless/β-catenin Wnt protein Wnt Signaling Pathway - drug effects β-Catenin |
| title | Niclosamide-loaded polymeric micelles ameliorate hepatocellular carcinoma in vivo through targeting Wnt and Notch pathways |
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