Folate-coated, long-circulating and pH-sensitive liposomes enhance doxorubicin antitumor effect in a breast cancer animal model
Long circulating pH-sensitive liposomes have been shown to effectively deliver doxorubicin (DOX) to tumors and reduce its toxic effects. Folic acid receptors are upregulated in a wide variety of solid, epithelial tumors, including breast cancer. In order to improve liposomal endocytosis and antitumo...
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| Veröffentlicht in: | Biomedicine & pharmacotherapy 2019-10, Vol.118, p.109323-109323, Article 109323 |
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| creator | de Oliveira Silva, Juliana Fernandes, Renata Salgado Ramos Oda, Caroline Mari Ferreira, Tiago Hilário Machado Botelho, Ana Flávia Martins Melo, Marília de Miranda, Marcelo Coutinho Assis Gomes, Dawidson Dantas Cassali, Geovanni Townsend, Danyelle M. Rubello, Domenico Oliveira, Mônica Cristina de Barros, André Luís Branco |
| description | Long circulating pH-sensitive liposomes have been shown to effectively deliver doxorubicin (DOX) to tumors and reduce its toxic effects. Folic acid receptors are upregulated in a wide variety of solid, epithelial tumors, including breast cancer. In order to improve liposomal endocytosis and antitumor activity, folic acid has been added to nanoparticles surfaces to exploit overexpression of folate receptors in tumor cells. The purpose of this study was to evaluate the antitumor activity in vitro and in vivo of long circulating pH-sensitive folate-coated DOX-loaded liposomes (SpHL-DOX-Fol) in a 4T1 breast cancer model system in vitro and in vivo. Biodistribution studies were performed and in vivo electrocardiographic parameters were evaluated. A higher tumor uptake for radiolabeled SpHL-Fol (99mTc-SpHL-Fol) 4 h after intravenous administration was observed in comparision with non-folate-coated liposomes (99mTc-SpHL). Antitumor activity showed that SpHL-DOX-Fol treatment led to a 68% growth arrest and drastically reduce pulmonary metastasis foci. Additionally, eletrocardiographic parameters analysis revealed no dispersion in the QT and QTc interval was observed in liposomal treated mice. In summary, this novel multifunctional nanoplatform deomonstrated higher tumor uptake and antitumor activity. SpHL-DOX-Fol represents a drug delivery platform to improve DOX tumor delivery and reduce dose-limiting toxicity. |
| doi_str_mv | 10.1016/j.biopha.2019.109323 |
| format | Article |
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Folic acid receptors are upregulated in a wide variety of solid, epithelial tumors, including breast cancer. In order to improve liposomal endocytosis and antitumor activity, folic acid has been added to nanoparticles surfaces to exploit overexpression of folate receptors in tumor cells. The purpose of this study was to evaluate the antitumor activity in vitro and in vivo of long circulating pH-sensitive folate-coated DOX-loaded liposomes (SpHL-DOX-Fol) in a 4T1 breast cancer model system in vitro and in vivo. Biodistribution studies were performed and in vivo electrocardiographic parameters were evaluated. A higher tumor uptake for radiolabeled SpHL-Fol (99mTc-SpHL-Fol) 4 h after intravenous administration was observed in comparision with non-folate-coated liposomes (99mTc-SpHL). Antitumor activity showed that SpHL-DOX-Fol treatment led to a 68% growth arrest and drastically reduce pulmonary metastasis foci. Additionally, eletrocardiographic parameters analysis revealed no dispersion in the QT and QTc interval was observed in liposomal treated mice. In summary, this novel multifunctional nanoplatform deomonstrated higher tumor uptake and antitumor activity. SpHL-DOX-Fol represents a drug delivery platform to improve DOX tumor delivery and reduce dose-limiting toxicity.</description><identifier>ISSN: 0753-3322</identifier><identifier>EISSN: 1950-6007</identifier><identifier>DOI: 10.1016/j.biopha.2019.109323</identifier><identifier>PMID: 31400669</identifier><language>eng</language><publisher>France: Elsevier Masson SAS</publisher><subject>Animals ; Antineoplastic Agents - pharmacology ; Antineoplastic Agents - therapeutic use ; Breast cancer ; Breast Neoplasms - diagnostic imaging ; Breast Neoplasms - drug therapy ; Breast Neoplasms - pathology ; Breast Neoplasms - ultrastructure ; Cardiotoxicity ; Cell Line, Tumor ; Cell Survival - drug effects ; Disease Models, Animal ; Doxorubicin ; Doxorubicin - blood ; Doxorubicin - pharmacology ; Doxorubicin - therapeutic use ; Female ; Folic acid ; Folic Acid - chemistry ; Hydrogen-Ion Concentration ; Liposomes ; Long-circulating liposome ; Mice, Inbred BALB C ; Neoplasm Metastasis ; pH-Sensitive liposome ; Tissue Distribution - drug effects</subject><ispartof>Biomedicine & pharmacotherapy, 2019-10, Vol.118, p.109323-109323, Article 109323</ispartof><rights>2019 The Authors</rights><rights>Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c430t-573605397ef485a7384be7f348e3019588fa709b6bcdbe51b3ece53a877ae55e3</citedby><cites>FETCH-LOGICAL-c430t-573605397ef485a7384be7f348e3019588fa709b6bcdbe51b3ece53a877ae55e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0753332219329774$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31400669$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>de Oliveira Silva, Juliana</creatorcontrib><creatorcontrib>Fernandes, Renata Salgado</creatorcontrib><creatorcontrib>Ramos Oda, Caroline Mari</creatorcontrib><creatorcontrib>Ferreira, Tiago Hilário</creatorcontrib><creatorcontrib>Machado Botelho, Ana Flávia</creatorcontrib><creatorcontrib>Martins Melo, Marília</creatorcontrib><creatorcontrib>de Miranda, Marcelo Coutinho</creatorcontrib><creatorcontrib>Assis Gomes, Dawidson</creatorcontrib><creatorcontrib>Dantas Cassali, Geovanni</creatorcontrib><creatorcontrib>Townsend, Danyelle M.</creatorcontrib><creatorcontrib>Rubello, Domenico</creatorcontrib><creatorcontrib>Oliveira, Mônica Cristina</creatorcontrib><creatorcontrib>de Barros, André Luís Branco</creatorcontrib><title>Folate-coated, long-circulating and pH-sensitive liposomes enhance doxorubicin antitumor effect in a breast cancer animal model</title><title>Biomedicine & pharmacotherapy</title><addtitle>Biomed Pharmacother</addtitle><description>Long circulating pH-sensitive liposomes have been shown to effectively deliver doxorubicin (DOX) to tumors and reduce its toxic effects. Folic acid receptors are upregulated in a wide variety of solid, epithelial tumors, including breast cancer. In order to improve liposomal endocytosis and antitumor activity, folic acid has been added to nanoparticles surfaces to exploit overexpression of folate receptors in tumor cells. The purpose of this study was to evaluate the antitumor activity in vitro and in vivo of long circulating pH-sensitive folate-coated DOX-loaded liposomes (SpHL-DOX-Fol) in a 4T1 breast cancer model system in vitro and in vivo. Biodistribution studies were performed and in vivo electrocardiographic parameters were evaluated. A higher tumor uptake for radiolabeled SpHL-Fol (99mTc-SpHL-Fol) 4 h after intravenous administration was observed in comparision with non-folate-coated liposomes (99mTc-SpHL). Antitumor activity showed that SpHL-DOX-Fol treatment led to a 68% growth arrest and drastically reduce pulmonary metastasis foci. Additionally, eletrocardiographic parameters analysis revealed no dispersion in the QT and QTc interval was observed in liposomal treated mice. In summary, this novel multifunctional nanoplatform deomonstrated higher tumor uptake and antitumor activity. SpHL-DOX-Fol represents a drug delivery platform to improve DOX tumor delivery and reduce dose-limiting toxicity.</description><subject>Animals</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - diagnostic imaging</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - pathology</subject><subject>Breast Neoplasms - ultrastructure</subject><subject>Cardiotoxicity</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival - drug effects</subject><subject>Disease Models, Animal</subject><subject>Doxorubicin</subject><subject>Doxorubicin - blood</subject><subject>Doxorubicin - pharmacology</subject><subject>Doxorubicin - therapeutic use</subject><subject>Female</subject><subject>Folic acid</subject><subject>Folic Acid - chemistry</subject><subject>Hydrogen-Ion Concentration</subject><subject>Liposomes</subject><subject>Long-circulating liposome</subject><subject>Mice, Inbred BALB C</subject><subject>Neoplasm Metastasis</subject><subject>pH-Sensitive liposome</subject><subject>Tissue Distribution - drug effects</subject><issn>0753-3322</issn><issn>1950-6007</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9Uctq4zAUFWVKmz7-oAz6gHF6FVmWvRkopS8odNOuhSRfJwq2ZCQnzKz661VIHzObbiQ495xzH4eQCwZzBqy6XM-NC-NKzxfAmgw1fMEPyIw1AooKQP4gM5CCF5wvFsfkJKU1AIiK10fkmLMSoKqaGXm9Db2esLAhv-0v2ge_LKyLdpNh55dU-5aO90VCn9zktkh7N4YUBkwU_Up7i7QNf0LcGGedz_TJTZshRIpdh3aiO4yaiDpN1O7oMXPcoHs6hBb7M3LY6T7h-ft_Sl5ub56v74vHp7uH66vHwpYcpkJIXoHgjcSurIWWvC4Nyo6XNfK8vqjrTktoTGVsa1Aww9Gi4LqWUqMQyE_J773vuDEDthb9FHWvxphHiX9V0E79X_FupZZhqySDsmYsG5R7AxtDShG7Ty0DtQtErdU-ELULRO0DybKf__b9FH0k8DUY5u23DqNK1mG-U-tivp9qg_u-wxsgkqH_</recordid><startdate>20191001</startdate><enddate>20191001</enddate><creator>de Oliveira Silva, Juliana</creator><creator>Fernandes, Renata Salgado</creator><creator>Ramos Oda, Caroline Mari</creator><creator>Ferreira, Tiago Hilário</creator><creator>Machado Botelho, Ana Flávia</creator><creator>Martins Melo, Marília</creator><creator>de Miranda, Marcelo Coutinho</creator><creator>Assis Gomes, Dawidson</creator><creator>Dantas Cassali, Geovanni</creator><creator>Townsend, Danyelle M.</creator><creator>Rubello, Domenico</creator><creator>Oliveira, Mônica Cristina</creator><creator>de Barros, André Luís Branco</creator><general>Elsevier Masson SAS</general><scope>6I.</scope><scope>AAFTH</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></search><sort><creationdate>20191001</creationdate><title>Folate-coated, long-circulating and pH-sensitive liposomes enhance doxorubicin antitumor effect in a breast cancer animal model</title><author>de Oliveira Silva, Juliana ; Fernandes, Renata Salgado ; Ramos Oda, Caroline Mari ; Ferreira, Tiago Hilário ; Machado Botelho, Ana Flávia ; Martins Melo, Marília ; de Miranda, Marcelo Coutinho ; Assis Gomes, Dawidson ; Dantas Cassali, Geovanni ; Townsend, Danyelle M. ; Rubello, Domenico ; Oliveira, Mônica Cristina ; de Barros, André Luís Branco</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c430t-573605397ef485a7384be7f348e3019588fa709b6bcdbe51b3ece53a877ae55e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - diagnostic imaging</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - pathology</topic><topic>Breast Neoplasms - ultrastructure</topic><topic>Cardiotoxicity</topic><topic>Cell Line, Tumor</topic><topic>Cell Survival - drug effects</topic><topic>Disease Models, Animal</topic><topic>Doxorubicin</topic><topic>Doxorubicin - blood</topic><topic>Doxorubicin - pharmacology</topic><topic>Doxorubicin - therapeutic use</topic><topic>Female</topic><topic>Folic acid</topic><topic>Folic Acid - chemistry</topic><topic>Hydrogen-Ion Concentration</topic><topic>Liposomes</topic><topic>Long-circulating liposome</topic><topic>Mice, Inbred BALB C</topic><topic>Neoplasm Metastasis</topic><topic>pH-Sensitive liposome</topic><topic>Tissue Distribution - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>de Oliveira Silva, Juliana</creatorcontrib><creatorcontrib>Fernandes, Renata Salgado</creatorcontrib><creatorcontrib>Ramos Oda, Caroline Mari</creatorcontrib><creatorcontrib>Ferreira, Tiago Hilário</creatorcontrib><creatorcontrib>Machado Botelho, Ana Flávia</creatorcontrib><creatorcontrib>Martins Melo, Marília</creatorcontrib><creatorcontrib>de Miranda, Marcelo Coutinho</creatorcontrib><creatorcontrib>Assis Gomes, Dawidson</creatorcontrib><creatorcontrib>Dantas Cassali, Geovanni</creatorcontrib><creatorcontrib>Townsend, Danyelle M.</creatorcontrib><creatorcontrib>Rubello, Domenico</creatorcontrib><creatorcontrib>Oliveira, Mônica Cristina</creatorcontrib><creatorcontrib>de Barros, André Luís Branco</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biomedicine & pharmacotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>de Oliveira Silva, Juliana</au><au>Fernandes, Renata Salgado</au><au>Ramos Oda, Caroline Mari</au><au>Ferreira, Tiago Hilário</au><au>Machado Botelho, Ana Flávia</au><au>Martins Melo, Marília</au><au>de Miranda, Marcelo Coutinho</au><au>Assis Gomes, Dawidson</au><au>Dantas Cassali, Geovanni</au><au>Townsend, Danyelle M.</au><au>Rubello, Domenico</au><au>Oliveira, Mônica Cristina</au><au>de Barros, André Luís Branco</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Folate-coated, long-circulating and pH-sensitive liposomes enhance doxorubicin antitumor effect in a breast cancer animal model</atitle><jtitle>Biomedicine & pharmacotherapy</jtitle><addtitle>Biomed Pharmacother</addtitle><date>2019-10-01</date><risdate>2019</risdate><volume>118</volume><spage>109323</spage><epage>109323</epage><pages>109323-109323</pages><artnum>109323</artnum><issn>0753-3322</issn><eissn>1950-6007</eissn><abstract>Long circulating pH-sensitive liposomes have been shown to effectively deliver doxorubicin (DOX) to tumors and reduce its toxic effects. Folic acid receptors are upregulated in a wide variety of solid, epithelial tumors, including breast cancer. In order to improve liposomal endocytosis and antitumor activity, folic acid has been added to nanoparticles surfaces to exploit overexpression of folate receptors in tumor cells. The purpose of this study was to evaluate the antitumor activity in vitro and in vivo of long circulating pH-sensitive folate-coated DOX-loaded liposomes (SpHL-DOX-Fol) in a 4T1 breast cancer model system in vitro and in vivo. Biodistribution studies were performed and in vivo electrocardiographic parameters were evaluated. A higher tumor uptake for radiolabeled SpHL-Fol (99mTc-SpHL-Fol) 4 h after intravenous administration was observed in comparision with non-folate-coated liposomes (99mTc-SpHL). Antitumor activity showed that SpHL-DOX-Fol treatment led to a 68% growth arrest and drastically reduce pulmonary metastasis foci. Additionally, eletrocardiographic parameters analysis revealed no dispersion in the QT and QTc interval was observed in liposomal treated mice. In summary, this novel multifunctional nanoplatform deomonstrated higher tumor uptake and antitumor activity. SpHL-DOX-Fol represents a drug delivery platform to improve DOX tumor delivery and reduce dose-limiting toxicity.</abstract><cop>France</cop><pub>Elsevier Masson SAS</pub><pmid>31400669</pmid><doi>10.1016/j.biopha.2019.109323</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Breast cancer Breast Neoplasms - diagnostic imaging Breast Neoplasms - drug therapy Breast Neoplasms - pathology Breast Neoplasms - ultrastructure Cardiotoxicity Cell Line, Tumor Cell Survival - drug effects Disease Models, Animal Doxorubicin Doxorubicin - blood Doxorubicin - pharmacology Doxorubicin - therapeutic use Female Folic acid Folic Acid - chemistry Hydrogen-Ion Concentration Liposomes Long-circulating liposome Mice, Inbred BALB C Neoplasm Metastasis pH-Sensitive liposome Tissue Distribution - drug effects |
| title | Folate-coated, long-circulating and pH-sensitive liposomes enhance doxorubicin antitumor effect in a breast cancer animal model |
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