Chemosensitizing indomethacin-conjugated dextran-based micelles for effective delivery of paclitaxel in resistant breast cancer therapy
Multidrug resistance (MDR) against chemotherapeutic agents has become the major obstacle to successful cancer therapy and multidrug resistance-associated proteins (MRPs) mediated drug efflux is the key factor for MDR. Indomethacin (IND), one of the non-steroidal anti-inflammatory agents, has been de...
Gespeichert in:
Veröffentlicht in: | PloS one 2017-07, Vol.12 (7), p.e0180037-e0180037 |
---|---|
Hauptverfasser: | , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | e0180037 |
---|---|
container_issue | 7 |
container_start_page | e0180037 |
container_title | PloS one |
container_volume | 12 |
creator | Ji, Weiping Wang, Bo Fan, Qiuping Xu, Chao He, Youwu Chen, Youfen |
description | Multidrug resistance (MDR) against chemotherapeutic agents has become the major obstacle to successful cancer therapy and multidrug resistance-associated proteins (MRPs) mediated drug efflux is the key factor for MDR. Indomethacin (IND), one of the non-steroidal anti-inflammatory agents, has been demonstrated to increase cytotoxic effects of anti-tumor agents as MRP substrates. In this study, dextran-g-indomethacin (DEX-IND) polymeric micelles were designed to delivery paclitaxel (PTX) for the treatment of MDR tumors. The DEX-IND polymer could effectively encapsulate PTX with high loading content and DEX-IND/PTX micelles present a small size distribution. Compared with free PTX, the release of PTX from DEX-IND/PTX micelles could be prolonged to 48 h. Cellular uptake test showed that the internalization of DEX-IND/PTX micelles by drug-sensitive MCF-7/ADR cells was significantly higher than free PTX benefiting from the inhibitory effect of IND on MRPs. In vitro cytotoxicity test further demonstrated that DEX-IND/PTX micelles could enhance the cytotoxicity of PTX against MCF-7/ADR tumor cells. In vivo pharmacokinetic results showed that DEX-IND/PTX micelles had longer systemic circulation time and slower plasma elimination rate in comparison to PTX. The anti-tumor efficacy test showed that DEX-IND/PTX micelles exhibited greater tumor growth-inhibition effects on MDR tumor-bearing mice, with good correlation between in vitro and in vivo. Overall, the cumulative evidence indicates that DEX-IND/PTX micelles hold significant promise for the treatment of MDR tumors. |
doi_str_mv | 10.1371/journal.pone.0180037 |
format | Article |
fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1916992417</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A497893574</galeid><doaj_id>oai_doaj_org_article_6532fcadfdd34db3a2a1efc5f22f1bf7</doaj_id><sourcerecordid>A497893574</sourcerecordid><originalsourceid>FETCH-LOGICAL-c692t-be9335c95631f2beaf70b9d39bae21352be4515d2399142e6a1451a3d04c02f93</originalsourceid><addsrcrecordid>eNqNk11rHCEUhofS0qRp_0FpBwqlvditH-PMelMIoR-BQKBft3JGj7sus7pRJyT9A_3bdbObkC25KF6ox-e86qunql5SMqW8ox-WYYwehuk6eJwSOiOEd4-qQyo5m7SM8Mf3xgfVs5SWhAg-a9un1QGbtbO2I81h9edkgauQ0CeX3W_n57XzJqwwL0A7P9HBL8c5ZDS1wascwU96SGW2chqHAVNtQ6zRWtTZXWKBhtLF6zrYeg16cBmucCiadcTkUgaf6z4ipFxr8BpjnRcYYX39vHpiYUj4YtcfVT8_f_px8nVydv7l9OT4bKJbyfKkR8m50FK0nFrWI9iO9NJw2QMyykUJNYIKw7iUtGHYAi1z4IY0mjAr-VH1equ7HkJSOw-TopK2UrKGdoU43RImwFKto1tBvFYBnLoJhDhXELPTA6pWcGY1GGsMb0zPgQFFq4VlzNLebrQ-7nYb-xUajb5YOOyJ7q94t1DzcKmEIFSQzXHf7QRiuBgxZbVyaeM8eAzjzbk73jLeiYK--Qd9-HY7ag7lAs7bUPbVG1F13MhuJrnomkJNH6BKM1gevnw460p8L-H9XkJhcvkvcxhTUqffv_0_e_5rn317j10gDHmRwjBmF3zaB5stqGNIKaK9M5kStamXWzfUpl7Url5K2qv7D3SXdFsg_C_3-BQk</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1916992417</pqid></control><display><type>article</type><title>Chemosensitizing indomethacin-conjugated dextran-based micelles for effective delivery of paclitaxel in resistant breast cancer therapy</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Public Library of Science (PLoS) Journals Open Access</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Ji, Weiping ; Wang, Bo ; Fan, Qiuping ; Xu, Chao ; He, Youwu ; Chen, Youfen</creator><contributor>Ahmad, Aamir</contributor><creatorcontrib>Ji, Weiping ; Wang, Bo ; Fan, Qiuping ; Xu, Chao ; He, Youwu ; Chen, Youfen ; Ahmad, Aamir</creatorcontrib><description>Multidrug resistance (MDR) against chemotherapeutic agents has become the major obstacle to successful cancer therapy and multidrug resistance-associated proteins (MRPs) mediated drug efflux is the key factor for MDR. Indomethacin (IND), one of the non-steroidal anti-inflammatory agents, has been demonstrated to increase cytotoxic effects of anti-tumor agents as MRP substrates. In this study, dextran-g-indomethacin (DEX-IND) polymeric micelles were designed to delivery paclitaxel (PTX) for the treatment of MDR tumors. The DEX-IND polymer could effectively encapsulate PTX with high loading content and DEX-IND/PTX micelles present a small size distribution. Compared with free PTX, the release of PTX from DEX-IND/PTX micelles could be prolonged to 48 h. Cellular uptake test showed that the internalization of DEX-IND/PTX micelles by drug-sensitive MCF-7/ADR cells was significantly higher than free PTX benefiting from the inhibitory effect of IND on MRPs. In vitro cytotoxicity test further demonstrated that DEX-IND/PTX micelles could enhance the cytotoxicity of PTX against MCF-7/ADR tumor cells. In vivo pharmacokinetic results showed that DEX-IND/PTX micelles had longer systemic circulation time and slower plasma elimination rate in comparison to PTX. The anti-tumor efficacy test showed that DEX-IND/PTX micelles exhibited greater tumor growth-inhibition effects on MDR tumor-bearing mice, with good correlation between in vitro and in vivo. Overall, the cumulative evidence indicates that DEX-IND/PTX micelles hold significant promise for the treatment of MDR tumors.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0180037</identifier><identifier>PMID: 28686704</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Anti-inflammatory agents ; Anticancer properties ; Bile ; Biocompatibility ; Biology and Life Sciences ; Breast cancer ; Breast Neoplasms - drug therapy ; Breast Neoplasms - pathology ; Cancer ; Cancer therapies ; Chemotherapy ; Circulation ; Cytotoxicity ; Dextran ; Dextrans - administration & dosage ; Dextrans - chemistry ; Dosage and administration ; Drug Delivery Systems ; Drug resistance ; Drug Resistance, Neoplasm - drug effects ; Drug therapy ; Efflux ; Encapsulation ; Female ; Hemodialysis ; Humans ; In vitro methods and tests ; In vivo methods and tests ; Indomethacin ; Indomethacin - administration & dosage ; Indomethacin - chemistry ; Inflammation ; Inhibition ; Internalization ; Laboratory animals ; Material requirements planning ; MCF-7 Cells ; Medicine and Health Sciences ; Mice ; Micelles ; MRP protein ; Multidrug resistance ; Nanoparticles ; Nonsteroidal anti-inflammatory drugs ; Orthopedics ; Paclitaxel ; Paclitaxel - administration & dosage ; Paclitaxel - chemistry ; Pharmacology ; Physical Sciences ; Polymers ; Proteins ; Quantum dots ; Rodents ; Size distribution ; Stress concentration ; Substrates ; Therapy ; Toxicity testing ; Tumor cells ; Tumors ; Xenograft Model Antitumor Assays</subject><ispartof>PloS one, 2017-07, Vol.12 (7), p.e0180037-e0180037</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Ji et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2017 Ji et al 2017 Ji et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-be9335c95631f2beaf70b9d39bae21352be4515d2399142e6a1451a3d04c02f93</citedby><cites>FETCH-LOGICAL-c692t-be9335c95631f2beaf70b9d39bae21352be4515d2399142e6a1451a3d04c02f93</cites><orcidid>0000-0003-1993-9109</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5501509/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5501509/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28686704$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Ahmad, Aamir</contributor><creatorcontrib>Ji, Weiping</creatorcontrib><creatorcontrib>Wang, Bo</creatorcontrib><creatorcontrib>Fan, Qiuping</creatorcontrib><creatorcontrib>Xu, Chao</creatorcontrib><creatorcontrib>He, Youwu</creatorcontrib><creatorcontrib>Chen, Youfen</creatorcontrib><title>Chemosensitizing indomethacin-conjugated dextran-based micelles for effective delivery of paclitaxel in resistant breast cancer therapy</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Multidrug resistance (MDR) against chemotherapeutic agents has become the major obstacle to successful cancer therapy and multidrug resistance-associated proteins (MRPs) mediated drug efflux is the key factor for MDR. Indomethacin (IND), one of the non-steroidal anti-inflammatory agents, has been demonstrated to increase cytotoxic effects of anti-tumor agents as MRP substrates. In this study, dextran-g-indomethacin (DEX-IND) polymeric micelles were designed to delivery paclitaxel (PTX) for the treatment of MDR tumors. The DEX-IND polymer could effectively encapsulate PTX with high loading content and DEX-IND/PTX micelles present a small size distribution. Compared with free PTX, the release of PTX from DEX-IND/PTX micelles could be prolonged to 48 h. Cellular uptake test showed that the internalization of DEX-IND/PTX micelles by drug-sensitive MCF-7/ADR cells was significantly higher than free PTX benefiting from the inhibitory effect of IND on MRPs. In vitro cytotoxicity test further demonstrated that DEX-IND/PTX micelles could enhance the cytotoxicity of PTX against MCF-7/ADR tumor cells. In vivo pharmacokinetic results showed that DEX-IND/PTX micelles had longer systemic circulation time and slower plasma elimination rate in comparison to PTX. The anti-tumor efficacy test showed that DEX-IND/PTX micelles exhibited greater tumor growth-inhibition effects on MDR tumor-bearing mice, with good correlation between in vitro and in vivo. Overall, the cumulative evidence indicates that DEX-IND/PTX micelles hold significant promise for the treatment of MDR tumors.</description><subject>Animals</subject><subject>Anti-inflammatory agents</subject><subject>Anticancer properties</subject><subject>Bile</subject><subject>Biocompatibility</subject><subject>Biology and Life Sciences</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - pathology</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Chemotherapy</subject><subject>Circulation</subject><subject>Cytotoxicity</subject><subject>Dextran</subject><subject>Dextrans - administration & dosage</subject><subject>Dextrans - chemistry</subject><subject>Dosage and administration</subject><subject>Drug Delivery Systems</subject><subject>Drug resistance</subject><subject>Drug Resistance, Neoplasm - drug effects</subject><subject>Drug therapy</subject><subject>Efflux</subject><subject>Encapsulation</subject><subject>Female</subject><subject>Hemodialysis</subject><subject>Humans</subject><subject>In vitro methods and tests</subject><subject>In vivo methods and tests</subject><subject>Indomethacin</subject><subject>Indomethacin - administration & dosage</subject><subject>Indomethacin - chemistry</subject><subject>Inflammation</subject><subject>Inhibition</subject><subject>Internalization</subject><subject>Laboratory animals</subject><subject>Material requirements planning</subject><subject>MCF-7 Cells</subject><subject>Medicine and Health Sciences</subject><subject>Mice</subject><subject>Micelles</subject><subject>MRP protein</subject><subject>Multidrug resistance</subject><subject>Nanoparticles</subject><subject>Nonsteroidal anti-inflammatory drugs</subject><subject>Orthopedics</subject><subject>Paclitaxel</subject><subject>Paclitaxel - administration & dosage</subject><subject>Paclitaxel - chemistry</subject><subject>Pharmacology</subject><subject>Physical Sciences</subject><subject>Polymers</subject><subject>Proteins</subject><subject>Quantum dots</subject><subject>Rodents</subject><subject>Size distribution</subject><subject>Stress concentration</subject><subject>Substrates</subject><subject>Therapy</subject><subject>Toxicity testing</subject><subject>Tumor cells</subject><subject>Tumors</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk11rHCEUhofS0qRp_0FpBwqlvditH-PMelMIoR-BQKBft3JGj7sus7pRJyT9A_3bdbObkC25KF6ox-e86qunql5SMqW8ox-WYYwehuk6eJwSOiOEd4-qQyo5m7SM8Mf3xgfVs5SWhAg-a9un1QGbtbO2I81h9edkgauQ0CeX3W_n57XzJqwwL0A7P9HBL8c5ZDS1wascwU96SGW2chqHAVNtQ6zRWtTZXWKBhtLF6zrYeg16cBmucCiadcTkUgaf6z4ipFxr8BpjnRcYYX39vHpiYUj4YtcfVT8_f_px8nVydv7l9OT4bKJbyfKkR8m50FK0nFrWI9iO9NJw2QMyykUJNYIKw7iUtGHYAi1z4IY0mjAr-VH1equ7HkJSOw-TopK2UrKGdoU43RImwFKto1tBvFYBnLoJhDhXELPTA6pWcGY1GGsMb0zPgQFFq4VlzNLebrQ-7nYb-xUajb5YOOyJ7q94t1DzcKmEIFSQzXHf7QRiuBgxZbVyaeM8eAzjzbk73jLeiYK--Qd9-HY7ag7lAs7bUPbVG1F13MhuJrnomkJNH6BKM1gevnw460p8L-H9XkJhcvkvcxhTUqffv_0_e_5rn317j10gDHmRwjBmF3zaB5stqGNIKaK9M5kStamXWzfUpl7Url5K2qv7D3SXdFsg_C_3-BQk</recordid><startdate>20170707</startdate><enddate>20170707</enddate><creator>Ji, Weiping</creator><creator>Wang, Bo</creator><creator>Fan, Qiuping</creator><creator>Xu, Chao</creator><creator>He, Youwu</creator><creator>Chen, Youfen</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-1993-9109</orcidid></search><sort><creationdate>20170707</creationdate><title>Chemosensitizing indomethacin-conjugated dextran-based micelles for effective delivery of paclitaxel in resistant breast cancer therapy</title><author>Ji, Weiping ; Wang, Bo ; Fan, Qiuping ; Xu, Chao ; He, Youwu ; Chen, Youfen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-be9335c95631f2beaf70b9d39bae21352be4515d2399142e6a1451a3d04c02f93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Anti-inflammatory agents</topic><topic>Anticancer properties</topic><topic>Bile</topic><topic>Biocompatibility</topic><topic>Biology and Life Sciences</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - pathology</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Chemotherapy</topic><topic>Circulation</topic><topic>Cytotoxicity</topic><topic>Dextran</topic><topic>Dextrans - administration & dosage</topic><topic>Dextrans - chemistry</topic><topic>Dosage and administration</topic><topic>Drug Delivery Systems</topic><topic>Drug resistance</topic><topic>Drug Resistance, Neoplasm - drug effects</topic><topic>Drug therapy</topic><topic>Efflux</topic><topic>Encapsulation</topic><topic>Female</topic><topic>Hemodialysis</topic><topic>Humans</topic><topic>In vitro methods and tests</topic><topic>In vivo methods and tests</topic><topic>Indomethacin</topic><topic>Indomethacin - administration & dosage</topic><topic>Indomethacin - chemistry</topic><topic>Inflammation</topic><topic>Inhibition</topic><topic>Internalization</topic><topic>Laboratory animals</topic><topic>Material requirements planning</topic><topic>MCF-7 Cells</topic><topic>Medicine and Health Sciences</topic><topic>Mice</topic><topic>Micelles</topic><topic>MRP protein</topic><topic>Multidrug resistance</topic><topic>Nanoparticles</topic><topic>Nonsteroidal anti-inflammatory drugs</topic><topic>Orthopedics</topic><topic>Paclitaxel</topic><topic>Paclitaxel - administration & dosage</topic><topic>Paclitaxel - chemistry</topic><topic>Pharmacology</topic><topic>Physical Sciences</topic><topic>Polymers</topic><topic>Proteins</topic><topic>Quantum dots</topic><topic>Rodents</topic><topic>Size distribution</topic><topic>Stress concentration</topic><topic>Substrates</topic><topic>Therapy</topic><topic>Toxicity testing</topic><topic>Tumor cells</topic><topic>Tumors</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ji, Weiping</creatorcontrib><creatorcontrib>Wang, Bo</creatorcontrib><creatorcontrib>Fan, Qiuping</creatorcontrib><creatorcontrib>Xu, Chao</creatorcontrib><creatorcontrib>He, Youwu</creatorcontrib><creatorcontrib>Chen, Youfen</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ji, Weiping</au><au>Wang, Bo</au><au>Fan, Qiuping</au><au>Xu, Chao</au><au>He, Youwu</au><au>Chen, Youfen</au><au>Ahmad, Aamir</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chemosensitizing indomethacin-conjugated dextran-based micelles for effective delivery of paclitaxel in resistant breast cancer therapy</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-07-07</date><risdate>2017</risdate><volume>12</volume><issue>7</issue><spage>e0180037</spage><epage>e0180037</epage><pages>e0180037-e0180037</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Multidrug resistance (MDR) against chemotherapeutic agents has become the major obstacle to successful cancer therapy and multidrug resistance-associated proteins (MRPs) mediated drug efflux is the key factor for MDR. Indomethacin (IND), one of the non-steroidal anti-inflammatory agents, has been demonstrated to increase cytotoxic effects of anti-tumor agents as MRP substrates. In this study, dextran-g-indomethacin (DEX-IND) polymeric micelles were designed to delivery paclitaxel (PTX) for the treatment of MDR tumors. The DEX-IND polymer could effectively encapsulate PTX with high loading content and DEX-IND/PTX micelles present a small size distribution. Compared with free PTX, the release of PTX from DEX-IND/PTX micelles could be prolonged to 48 h. Cellular uptake test showed that the internalization of DEX-IND/PTX micelles by drug-sensitive MCF-7/ADR cells was significantly higher than free PTX benefiting from the inhibitory effect of IND on MRPs. In vitro cytotoxicity test further demonstrated that DEX-IND/PTX micelles could enhance the cytotoxicity of PTX against MCF-7/ADR tumor cells. In vivo pharmacokinetic results showed that DEX-IND/PTX micelles had longer systemic circulation time and slower plasma elimination rate in comparison to PTX. The anti-tumor efficacy test showed that DEX-IND/PTX micelles exhibited greater tumor growth-inhibition effects on MDR tumor-bearing mice, with good correlation between in vitro and in vivo. Overall, the cumulative evidence indicates that DEX-IND/PTX micelles hold significant promise for the treatment of MDR tumors.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28686704</pmid><doi>10.1371/journal.pone.0180037</doi><orcidid>https://orcid.org/0000-0003-1993-9109</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2017-07, Vol.12 (7), p.e0180037-e0180037 |
issn | 1932-6203 1932-6203 |
language | eng |
recordid | cdi_plos_journals_1916992417 |
source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
subjects | Animals Anti-inflammatory agents Anticancer properties Bile Biocompatibility Biology and Life Sciences Breast cancer Breast Neoplasms - drug therapy Breast Neoplasms - pathology Cancer Cancer therapies Chemotherapy Circulation Cytotoxicity Dextran Dextrans - administration & dosage Dextrans - chemistry Dosage and administration Drug Delivery Systems Drug resistance Drug Resistance, Neoplasm - drug effects Drug therapy Efflux Encapsulation Female Hemodialysis Humans In vitro methods and tests In vivo methods and tests Indomethacin Indomethacin - administration & dosage Indomethacin - chemistry Inflammation Inhibition Internalization Laboratory animals Material requirements planning MCF-7 Cells Medicine and Health Sciences Mice Micelles MRP protein Multidrug resistance Nanoparticles Nonsteroidal anti-inflammatory drugs Orthopedics Paclitaxel Paclitaxel - administration & dosage Paclitaxel - chemistry Pharmacology Physical Sciences Polymers Proteins Quantum dots Rodents Size distribution Stress concentration Substrates Therapy Toxicity testing Tumor cells Tumors Xenograft Model Antitumor Assays |
title | Chemosensitizing indomethacin-conjugated dextran-based micelles for effective delivery of paclitaxel in resistant breast cancer therapy |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-03T05%3A04%3A37IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Chemosensitizing%20indomethacin-conjugated%20dextran-based%20micelles%20for%20effective%20delivery%20of%20paclitaxel%20in%20resistant%20breast%20cancer%20therapy&rft.jtitle=PloS%20one&rft.au=Ji,%20Weiping&rft.date=2017-07-07&rft.volume=12&rft.issue=7&rft.spage=e0180037&rft.epage=e0180037&rft.pages=e0180037-e0180037&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0180037&rft_dat=%3Cgale_plos_%3EA497893574%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1916992417&rft_id=info:pmid/28686704&rft_galeid=A497893574&rft_doaj_id=oai_doaj_org_article_6532fcadfdd34db3a2a1efc5f22f1bf7&rfr_iscdi=true |