Selective delivery of doxorubicin by novel stimuli-sensitive nano-ferritins overcomes tumor refractoriness
Human ferritin heavy chain (HFt) has been demonstrated to possess considerable potential for targeted delivery of drugs and diagnostic agents to cancer cells. Here, we report the development of a novel HFt-based genetic construct (HFt-MP-PAS) containing a short peptide linker (MP) between each HFt s...
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| Veröffentlicht in: | Journal of controlled release 2016-10, Vol.239, p.10-18 |
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| creator | Fracasso, Giulio Falvo, Elisabetta Colotti, Gianni Fazi, Francesco Ingegnere, Tiziano Amalfitano, Adriana Doglietto, Giovanni Battista Alfieri, Sergio Boffi, Alberto Morea, Veronica Conti, Giamaica Tremante, Elisa Giacomini, Patrizio Arcovito, Alessandro Ceci, Pierpaolo |
| description | Human ferritin heavy chain (HFt) has been demonstrated to possess considerable potential for targeted delivery of drugs and diagnostic agents to cancer cells. Here, we report the development of a novel HFt-based genetic construct (HFt-MP-PAS) containing a short peptide linker (MP) between each HFt subunit and an outer shielding polypeptide sequence rich in proline (P), serine (S) and alanine (A) residues (PAS). The peptide linker contains a matrix-metalloproteinases (MMPs) cleavage site that permits the protective PAS shield to be removed by tumor-driven proteolytic cleavage within the tumor microenvironment. For the first time HFt-MP-PAS ability to deliver doxorubicin to cancer cells, subcellular localization, and therapeutic efficacy on a xenogeneic mouse model of a highly refractory to conventional chemotherapeutics type of cancer were evaluated. HFt-MP-PAS-DOXO performance was compared with the novel albumin-based drug delivery system INNO-206, currently in phase III clinical trials. The results of this work provide solid evidence indicating that the stimuli-sensitive, long-circulating HFt-MP-PAS nanocarriers described herein have the potential to be exploited in cancer therapy.
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| doi_str_mv | 10.1016/j.jconrel.2016.08.010 |
| format | Article |
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[Display omitted]</description><subject>Animals</subject><subject>Antibiotics, Antineoplastic - administration & dosage</subject><subject>Apoferritins - administration & dosage</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Doxorubicin - administration & dosage</subject><subject>Drug Carriers - administration & dosage</subject><subject>Drug Delivery Systems - methods</subject><subject>Drug-delivery</subject><subject>Female</subject><subject>Ferritin</subject><subject>Humans</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Nanoparticles - administration & dosage</subject><subject>Nuclear localization</subject><subject>Pancreatic cancer</subject><subject>PASylation</subject><subject>Protein-cage nanocarrier</subject><subject>Xenograft Model Antitumor Assays - methods</subject><issn>0168-3659</issn><issn>1873-4995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1LxDAQhoMo7vrxE5QcvbRO0qZNTyLiFyx4UM-hTaeQ0iZr0i7uvze6q1dPwzDPO5M8hFwwSBmw4rpPe-2sxyHlsU1BpsDggCyZLLMkrypxSJZxIJOsENWCnITQA4DI8vKYLHgpeM4lX5L-FQfUk9kgbXGIxW-p62jrPp2fG6ONpc2WWrfBgYbJjPNgkoA2mJ-Ira1LOvQ-tjbQSHntRgx0mkfnqcfO13py3lgM4YwcdfUQ8HxfT8n7w_3b3VOyenl8vrtdJTpnfEoQijYH1KXooJZYsRKaTmhWA29yVgjNi6LNWMMk1Blgq2VRVrlkDTSi6zjLTsnVbu_au48Zw6RGEzQOQ23RzUExybMKykpARMUO1d6FEJ-r1t6Mtd8qBupbs-rVXrP61qxAqqg55i73J-ZmxPYv9es1Ajc7AONHNwa9Ctqg1dgaH3Wr1pl_TnwBIPiT0A</recordid><startdate>20161010</startdate><enddate>20161010</enddate><creator>Fracasso, Giulio</creator><creator>Falvo, Elisabetta</creator><creator>Colotti, Gianni</creator><creator>Fazi, Francesco</creator><creator>Ingegnere, Tiziano</creator><creator>Amalfitano, Adriana</creator><creator>Doglietto, Giovanni Battista</creator><creator>Alfieri, Sergio</creator><creator>Boffi, Alberto</creator><creator>Morea, Veronica</creator><creator>Conti, Giamaica</creator><creator>Tremante, Elisa</creator><creator>Giacomini, Patrizio</creator><creator>Arcovito, Alessandro</creator><creator>Ceci, Pierpaolo</creator><general>Elsevier B.V</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>7X8</scope><orcidid>https://orcid.org/0000-0001-7712-8430</orcidid><orcidid>https://orcid.org/0000-0003-3024-0307</orcidid></search><sort><creationdate>20161010</creationdate><title>Selective delivery of doxorubicin by novel stimuli-sensitive nano-ferritins overcomes tumor refractoriness</title><author>Fracasso, Giulio ; Falvo, Elisabetta ; Colotti, Gianni ; Fazi, Francesco ; Ingegnere, Tiziano ; Amalfitano, Adriana ; Doglietto, Giovanni Battista ; Alfieri, Sergio ; Boffi, Alberto ; Morea, Veronica ; Conti, Giamaica ; Tremante, Elisa ; Giacomini, Patrizio ; Arcovito, Alessandro ; Ceci, Pierpaolo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-e06d40ec75f0a8e9170bf5c1a02b4165c266d31b180a30edc8679481b0b5ff213</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Antibiotics, Antineoplastic - administration & dosage</topic><topic>Apoferritins - administration & dosage</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Doxorubicin - administration & dosage</topic><topic>Drug Carriers - administration & dosage</topic><topic>Drug Delivery Systems - methods</topic><topic>Drug-delivery</topic><topic>Female</topic><topic>Ferritin</topic><topic>Humans</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Nanoparticles - administration & dosage</topic><topic>Nuclear localization</topic><topic>Pancreatic cancer</topic><topic>PASylation</topic><topic>Protein-cage nanocarrier</topic><topic>Xenograft Model Antitumor Assays - methods</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fracasso, Giulio</creatorcontrib><creatorcontrib>Falvo, Elisabetta</creatorcontrib><creatorcontrib>Colotti, Gianni</creatorcontrib><creatorcontrib>Fazi, Francesco</creatorcontrib><creatorcontrib>Ingegnere, Tiziano</creatorcontrib><creatorcontrib>Amalfitano, Adriana</creatorcontrib><creatorcontrib>Doglietto, Giovanni Battista</creatorcontrib><creatorcontrib>Alfieri, Sergio</creatorcontrib><creatorcontrib>Boffi, Alberto</creatorcontrib><creatorcontrib>Morea, Veronica</creatorcontrib><creatorcontrib>Conti, Giamaica</creatorcontrib><creatorcontrib>Tremante, Elisa</creatorcontrib><creatorcontrib>Giacomini, Patrizio</creatorcontrib><creatorcontrib>Arcovito, Alessandro</creatorcontrib><creatorcontrib>Ceci, Pierpaolo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of controlled release</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fracasso, Giulio</au><au>Falvo, Elisabetta</au><au>Colotti, Gianni</au><au>Fazi, Francesco</au><au>Ingegnere, Tiziano</au><au>Amalfitano, Adriana</au><au>Doglietto, Giovanni Battista</au><au>Alfieri, Sergio</au><au>Boffi, Alberto</au><au>Morea, Veronica</au><au>Conti, Giamaica</au><au>Tremante, Elisa</au><au>Giacomini, Patrizio</au><au>Arcovito, Alessandro</au><au>Ceci, Pierpaolo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Selective delivery of doxorubicin by novel stimuli-sensitive nano-ferritins overcomes tumor refractoriness</atitle><jtitle>Journal of controlled release</jtitle><addtitle>J Control Release</addtitle><date>2016-10-10</date><risdate>2016</risdate><volume>239</volume><spage>10</spage><epage>18</epage><pages>10-18</pages><issn>0168-3659</issn><eissn>1873-4995</eissn><abstract>Human ferritin heavy chain (HFt) has been demonstrated to possess considerable potential for targeted delivery of drugs and diagnostic agents to cancer cells. Here, we report the development of a novel HFt-based genetic construct (HFt-MP-PAS) containing a short peptide linker (MP) between each HFt subunit and an outer shielding polypeptide sequence rich in proline (P), serine (S) and alanine (A) residues (PAS). The peptide linker contains a matrix-metalloproteinases (MMPs) cleavage site that permits the protective PAS shield to be removed by tumor-driven proteolytic cleavage within the tumor microenvironment. For the first time HFt-MP-PAS ability to deliver doxorubicin to cancer cells, subcellular localization, and therapeutic efficacy on a xenogeneic mouse model of a highly refractory to conventional chemotherapeutics type of cancer were evaluated. HFt-MP-PAS-DOXO performance was compared with the novel albumin-based drug delivery system INNO-206, currently in phase III clinical trials. The results of this work provide solid evidence indicating that the stimuli-sensitive, long-circulating HFt-MP-PAS nanocarriers described herein have the potential to be exploited in cancer therapy.
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| identifier | ISSN: 0168-3659 |
| ispartof | Journal of controlled release, 2016-10, Vol.239, p.10-18 |
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| subjects | Animals Antibiotics, Antineoplastic - administration & dosage Apoferritins - administration & dosage Cell Line, Tumor Cell Proliferation - drug effects Doxorubicin - administration & dosage Drug Carriers - administration & dosage Drug Delivery Systems - methods Drug-delivery Female Ferritin Humans Mice Mice, Nude Nanoparticles - administration & dosage Nuclear localization Pancreatic cancer PASylation Protein-cage nanocarrier Xenograft Model Antitumor Assays - methods |
| title | Selective delivery of doxorubicin by novel stimuli-sensitive nano-ferritins overcomes tumor refractoriness |
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