Development of an oral nanotherapeutics using redox nanoparticles for treatment of colitis-associated colon cancer
Abstract Oral chemotherapy is the preferred treatment for colon cancer. However, this strategy faces many challenges, including instability in the gastrointestinal (GI) tract, insufficient bioavailability, low tumor targeting, and severe adverse effects. In this study, we designed a novel redox nano...
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| Veröffentlicht in: | Biomaterials 2015-07, Vol.55, p.54-63 |
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| creator | Vong, Long Binh Yoshitomi, Toru Matsui, Hirofumi Nagasaki, Yukio |
| description | Abstract Oral chemotherapy is the preferred treatment for colon cancer. However, this strategy faces many challenges, including instability in the gastrointestinal (GI) tract, insufficient bioavailability, low tumor targeting, and severe adverse effects. In this study, we designed a novel redox nanoparticle (RNPO ) that is an ideal oral therapeutics for colitis-associated colon cancer treatment. RNPO possesses nitroxide radicals in the core, which act as reactive oxygen species (ROS) scavengers. Orally administered RNPO highly accumulated in colonic mucosa, and specifically internalized in cancer tissues, but less in normal tissues. Despite of long-term oral administration of RNPO , no noticeable toxicities were observed in major organs of mice. Because RNPO effectively scavenged ROS, it significantly suppressed tumor growth after accumulation at tumor sites. Combination of RNPO with the conventional chemotherapy, irinotecan, led to remarkably improved therapeutic efficacy and effectively suppressed its adverse effects on GI tract. Therefore, RNPO is promising oral nanotherapeutics for cancer therapies. |
| doi_str_mv | 10.1016/j.biomaterials.2015.03.037 |
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However, this strategy faces many challenges, including instability in the gastrointestinal (GI) tract, insufficient bioavailability, low tumor targeting, and severe adverse effects. In this study, we designed a novel redox nanoparticle (RNPO ) that is an ideal oral therapeutics for colitis-associated colon cancer treatment. RNPO possesses nitroxide radicals in the core, which act as reactive oxygen species (ROS) scavengers. Orally administered RNPO highly accumulated in colonic mucosa, and specifically internalized in cancer tissues, but less in normal tissues. Despite of long-term oral administration of RNPO , no noticeable toxicities were observed in major organs of mice. Because RNPO effectively scavenged ROS, it significantly suppressed tumor growth after accumulation at tumor sites. Combination of RNPO with the conventional chemotherapy, irinotecan, led to remarkably improved therapeutic efficacy and effectively suppressed its adverse effects on GI tract. Therefore, RNPO is promising oral nanotherapeutics for cancer therapies.</description><identifier>ISSN: 0142-9612</identifier><identifier>EISSN: 1878-5905</identifier><identifier>DOI: 10.1016/j.biomaterials.2015.03.037</identifier><identifier>PMID: 25934452</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Administration, Oral ; Advanced Basic Science ; Animals ; Antineoplastic Agents - chemistry ; Azoxymethane - administration & dosage ; Camptothecin - analogs & derivatives ; Camptothecin - chemistry ; Cancer ; Cell Line, Tumor ; Chemotherapy ; Colitis - complications ; Colitis - therapy ; Colon ; Colonic Neoplasms - complications ; Colonic Neoplasms - therapy ; Dentistry ; Dextrans - chemistry ; Drug delivery system ; Drug Delivery Systems ; Drug Screening Assays, Antitumor ; Endoscopy ; Free Radical Scavengers - chemistry ; Inflammation - pathology ; Male ; Mice ; Mice, Inbred ICR ; Nanomedicine - methods ; Nanoparticles ; Nanoparticles - chemistry ; Nanostructure ; Neoplasms, Experimental - therapy ; Nitrogen Oxides - chemistry ; Oral therapeutics ; Oxidation-Reduction ; Reactive Oxygen Species - chemistry ; Redox nanoparticles ; ROS ; Sulfates - chemistry ; Toxicity ; Tumors</subject><ispartof>Biomaterials, 2015-07, Vol.55, p.54-63</ispartof><rights>Elsevier Ltd</rights><rights>2015 Elsevier Ltd</rights><rights>Copyright © 2015 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c567t-27ddd55e1a752921ef08a9b37cdca8c4c6080ebc7007f7c1b97f3c4d81ca249c3</citedby><cites>FETCH-LOGICAL-c567t-27ddd55e1a752921ef08a9b37cdca8c4c6080ebc7007f7c1b97f3c4d81ca249c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0142961215003154$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25934452$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vong, Long Binh</creatorcontrib><creatorcontrib>Yoshitomi, Toru</creatorcontrib><creatorcontrib>Matsui, Hirofumi</creatorcontrib><creatorcontrib>Nagasaki, Yukio</creatorcontrib><title>Development of an oral nanotherapeutics using redox nanoparticles for treatment of colitis-associated colon cancer</title><title>Biomaterials</title><addtitle>Biomaterials</addtitle><description>Abstract Oral chemotherapy is the preferred treatment for colon cancer. However, this strategy faces many challenges, including instability in the gastrointestinal (GI) tract, insufficient bioavailability, low tumor targeting, and severe adverse effects. In this study, we designed a novel redox nanoparticle (RNPO ) that is an ideal oral therapeutics for colitis-associated colon cancer treatment. RNPO possesses nitroxide radicals in the core, which act as reactive oxygen species (ROS) scavengers. Orally administered RNPO highly accumulated in colonic mucosa, and specifically internalized in cancer tissues, but less in normal tissues. Despite of long-term oral administration of RNPO , no noticeable toxicities were observed in major organs of mice. Because RNPO effectively scavenged ROS, it significantly suppressed tumor growth after accumulation at tumor sites. Combination of RNPO with the conventional chemotherapy, irinotecan, led to remarkably improved therapeutic efficacy and effectively suppressed its adverse effects on GI tract. Therefore, RNPO is promising oral nanotherapeutics for cancer therapies.</description><subject>Administration, Oral</subject><subject>Advanced Basic Science</subject><subject>Animals</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Azoxymethane - administration & dosage</subject><subject>Camptothecin - analogs & derivatives</subject><subject>Camptothecin - chemistry</subject><subject>Cancer</subject><subject>Cell Line, Tumor</subject><subject>Chemotherapy</subject><subject>Colitis - complications</subject><subject>Colitis - therapy</subject><subject>Colon</subject><subject>Colonic Neoplasms - complications</subject><subject>Colonic Neoplasms - therapy</subject><subject>Dentistry</subject><subject>Dextrans - chemistry</subject><subject>Drug delivery system</subject><subject>Drug Delivery Systems</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Endoscopy</subject><subject>Free Radical Scavengers - chemistry</subject><subject>Inflammation - pathology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred ICR</subject><subject>Nanomedicine - methods</subject><subject>Nanoparticles</subject><subject>Nanoparticles - chemistry</subject><subject>Nanostructure</subject><subject>Neoplasms, Experimental - therapy</subject><subject>Nitrogen Oxides - chemistry</subject><subject>Oral therapeutics</subject><subject>Oxidation-Reduction</subject><subject>Reactive Oxygen Species - chemistry</subject><subject>Redox nanoparticles</subject><subject>ROS</subject><subject>Sulfates - chemistry</subject><subject>Toxicity</subject><subject>Tumors</subject><issn>0142-9612</issn><issn>1878-5905</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUsFu1TAQtBCIPgq_gCxOXPJqO3GccEBCLVCkShyAs-WsN-BHYgfbqdq_x-G1CHGqtJLl3dnZ1cwS8oqzPWe8PTvsBxdmkzE6M6W9YFzuWV1CPSI73qmukj2Tj8mO8UZUfcvFCXmW0oGVP2vEU3IiZF83jRQ7Ei_wGqewzOgzDSM1noZoJuqND_kHRrPgmh0kuibnv9OINtz8KS4mlvyEiY4h0hzR5HsOCJPLLlUmpQCu7Gm3VPAUjAeMz8mTseyNL-7eU_Ltw_uv55fV1eePn87fXVUgW5Uroay1UiI3SopecBxZZ_qhVmDBdNBAyzqGAyjG1KiAD70aa2hsx8GIpof6lLw-8i4x_FoxZT27BDhNxmNYk-ZKsZq3nIsHQGvRCdHzvkDfHKEQQ0oRR71EN5t4qznTmz36oP-1R2_2aFaXUKX55d2cdZjR_m2996MALo4ALMJcO4w6gcOimnURIWsb3MPmvP2PBibnHZjpJ95iOoQ1-q2H6yQ001-2Q9nuhEtWJJFN_Rs3Mr9x</recordid><startdate>20150701</startdate><enddate>20150701</enddate><creator>Vong, Long Binh</creator><creator>Yoshitomi, Toru</creator><creator>Matsui, Hirofumi</creator><creator>Nagasaki, Yukio</creator><general>Elsevier Ltd</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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7SR</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>F28</scope><scope>JG9</scope><scope>L7M</scope></search><sort><creationdate>20150701</creationdate><title>Development of an oral nanotherapeutics using redox nanoparticles for treatment of colitis-associated colon cancer</title><author>Vong, Long Binh ; Yoshitomi, Toru ; Matsui, Hirofumi ; Nagasaki, Yukio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c567t-27ddd55e1a752921ef08a9b37cdca8c4c6080ebc7007f7c1b97f3c4d81ca249c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Administration, Oral</topic><topic>Advanced Basic Science</topic><topic>Animals</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Azoxymethane - administration & dosage</topic><topic>Camptothecin - analogs & derivatives</topic><topic>Camptothecin - chemistry</topic><topic>Cancer</topic><topic>Cell Line, Tumor</topic><topic>Chemotherapy</topic><topic>Colitis - complications</topic><topic>Colitis - therapy</topic><topic>Colon</topic><topic>Colonic Neoplasms - complications</topic><topic>Colonic Neoplasms - therapy</topic><topic>Dentistry</topic><topic>Dextrans - chemistry</topic><topic>Drug delivery system</topic><topic>Drug Delivery Systems</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Endoscopy</topic><topic>Free Radical Scavengers - chemistry</topic><topic>Inflammation - pathology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred ICR</topic><topic>Nanomedicine - methods</topic><topic>Nanoparticles</topic><topic>Nanoparticles - chemistry</topic><topic>Nanostructure</topic><topic>Neoplasms, Experimental - therapy</topic><topic>Nitrogen Oxides - chemistry</topic><topic>Oral therapeutics</topic><topic>Oxidation-Reduction</topic><topic>Reactive Oxygen Species - chemistry</topic><topic>Redox nanoparticles</topic><topic>ROS</topic><topic>Sulfates - chemistry</topic><topic>Toxicity</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vong, Long Binh</creatorcontrib><creatorcontrib>Yoshitomi, Toru</creatorcontrib><creatorcontrib>Matsui, Hirofumi</creatorcontrib><creatorcontrib>Nagasaki, Yukio</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><jtitle>Biomaterials</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vong, Long Binh</au><au>Yoshitomi, Toru</au><au>Matsui, Hirofumi</au><au>Nagasaki, Yukio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Development of an oral nanotherapeutics using redox nanoparticles for treatment of colitis-associated colon cancer</atitle><jtitle>Biomaterials</jtitle><addtitle>Biomaterials</addtitle><date>2015-07-01</date><risdate>2015</risdate><volume>55</volume><spage>54</spage><epage>63</epage><pages>54-63</pages><issn>0142-9612</issn><eissn>1878-5905</eissn><abstract>Abstract Oral chemotherapy is the preferred treatment for colon cancer. However, this strategy faces many challenges, including instability in the gastrointestinal (GI) tract, insufficient bioavailability, low tumor targeting, and severe adverse effects. In this study, we designed a novel redox nanoparticle (RNPO ) that is an ideal oral therapeutics for colitis-associated colon cancer treatment. RNPO possesses nitroxide radicals in the core, which act as reactive oxygen species (ROS) scavengers. Orally administered RNPO highly accumulated in colonic mucosa, and specifically internalized in cancer tissues, but less in normal tissues. Despite of long-term oral administration of RNPO , no noticeable toxicities were observed in major organs of mice. Because RNPO effectively scavenged ROS, it significantly suppressed tumor growth after accumulation at tumor sites. Combination of RNPO with the conventional chemotherapy, irinotecan, led to remarkably improved therapeutic efficacy and effectively suppressed its adverse effects on GI tract. 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| subjects | Administration, Oral Advanced Basic Science Animals Antineoplastic Agents - chemistry Azoxymethane - administration & dosage Camptothecin - analogs & derivatives Camptothecin - chemistry Cancer Cell Line, Tumor Chemotherapy Colitis - complications Colitis - therapy Colon Colonic Neoplasms - complications Colonic Neoplasms - therapy Dentistry Dextrans - chemistry Drug delivery system Drug Delivery Systems Drug Screening Assays, Antitumor Endoscopy Free Radical Scavengers - chemistry Inflammation - pathology Male Mice Mice, Inbred ICR Nanomedicine - methods Nanoparticles Nanoparticles - chemistry Nanostructure Neoplasms, Experimental - therapy Nitrogen Oxides - chemistry Oral therapeutics Oxidation-Reduction Reactive Oxygen Species - chemistry Redox nanoparticles ROS Sulfates - chemistry Toxicity Tumors |
| title | Development of an oral nanotherapeutics using redox nanoparticles for treatment of colitis-associated colon cancer |
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