Co-Delivery of Docetaxel and Salinomycin to Target Both Breast Cancer Cells and Stem Cells by PLGA/TPGS Nanoparticles
Identifieur interne : 000633 ( Pmc/Curation ); précédent : 000632; suivant : 000634Co-Delivery of Docetaxel and Salinomycin to Target Both Breast Cancer Cells and Stem Cells by PLGA/TPGS Nanoparticles
Auteurs : Jie Gao [République populaire de Chine] ; Junjie Liu [République populaire de Chine] ; Fangyuan Xie [République populaire de Chine] ; Ying Lu [République populaire de Chine] ; Chuan Yin [République populaire de Chine] ; Xian Shen [République populaire de Chine]Source :
- International Journal of Nanomedicine [ 1176-9114 ] ; 2019.
Abstract
Conventional chemotherapy is hampered by the presence of breast cancer stem cells (BCSCs). It is crucial to eradicating both the bulky breast cancer cells and BCSCs, using a combination of conventional chemotherapy and anti-CSCs drugs. However, the synergistic ratio of drug combinations cannot be easily maintained in vivo. In our previous studies, we demonstrated that the simultaneous delivery of two drugs via nanoliposomes could maintain the synergistic drug ratio for 12 h in vivo. However, nanoliposomes have the disadvantage of quick drug release, which makes it difficult to maintain the synergistic drug ratio for a long time. Herein, we developed a co-delivery system for docetaxel (DTX)—a first-line chemotherapy drug for breast cancer—and salinomycin (SAL)—an anti-BCSCs drug—in rigid nanoparticles constituted of polylactide-co-glycolide/D-alpha-tocopherol polyethylene glycol 1000 succinate (PLGA/TPGS).
Nanoparticles loaded with SAL and DTX at the optimized ratio (NSD) were prepared by the nanoprecipitation method. The characterization, cellular uptake, and cytotoxicity of nanoparticles were investigated in vitro, and the pharmacokinetics, tissue distribution, antitumor and anti-CSCs activity of nanoparticles were evaluated in vivo.
We demonstrated that a SAL/DTX molar ratio of 1:1 was synergistic in MCF-7 cells and MCF-7-MS. Moreover, the enhanced internalization of nanoparticles was observed in MCF-7 cells and MCF-7-MS. Furthermore, the cytotoxicity of NSD against both MCF-7 cells and MCF-7-MS was stronger than the cytotoxicity of any single treatment in vitro. Significantly, NSD could prolong the circulation time and maintain the synergistic ratio of SAL to DTX in vivo for 24 h, thus exhibiting superior tumor targeting and anti-tumor activity compared to other treatments.
Co-encapsulation of SAL and DTX in PLGA/TPGS nanoparticles could maintain the synergistic ratio of drugs in vivo in a better manner; thus, providing a promising strategy for synergistic inhibition of breast cancer.
Url:
DOI: 10.2147/IJN.S230376
PubMed: 32063706
PubMed Central: 6884979
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PMC:6884979Le document en format XML
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<author><name sortKey="Liu, Junjie" sort="Liu, Junjie" uniqKey="Liu J" first="Junjie" last="Liu">Junjie Liu</name>
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<author><name sortKey="Xie, Fangyuan" sort="Xie, Fangyuan" uniqKey="Xie F" first="Fangyuan" last="Xie">Fangyuan Xie</name>
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<author><name sortKey="Lu, Ying" sort="Lu, Ying" uniqKey="Lu Y" first="Ying" last="Lu">Ying Lu</name>
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<author><name sortKey="Yin, Chuan" sort="Yin, Chuan" uniqKey="Yin C" first="Chuan" last="Yin">Chuan Yin</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Co-Delivery of Docetaxel and Salinomycin to Target Both Breast Cancer Cells and Stem Cells by PLGA/TPGS Nanoparticles</title>
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</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
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<author><name sortKey="Xie, Fangyuan" sort="Xie, Fangyuan" uniqKey="Xie F" first="Fangyuan" last="Xie">Fangyuan Xie</name>
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<author><name sortKey="Lu, Ying" sort="Lu, Ying" uniqKey="Lu Y" first="Ying" last="Lu">Ying Lu</name>
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<author><name sortKey="Yin, Chuan" sort="Yin, Chuan" uniqKey="Yin C" first="Chuan" last="Yin">Chuan Yin</name>
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<author><name sortKey="Shen, Xian" sort="Shen, Xian" uniqKey="Shen X" first="Xian" last="Shen">Xian Shen</name>
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,<country>People’s Republic of China</country>
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<front><div type="abstract" xml:lang="en"><sec id="S2001"><title>Purpose</title>
<p>Conventional chemotherapy is hampered by the presence of breast cancer stem cells (BCSCs). It is crucial to eradicating both the bulky breast cancer cells and BCSCs, using a combination of conventional chemotherapy and anti-CSCs drugs. However, the synergistic ratio of drug combinations cannot be easily maintained in vivo. In our previous studies, we demonstrated that the simultaneous delivery of two drugs via nanoliposomes could maintain the synergistic drug ratio for 12 h in vivo. However, nanoliposomes have the disadvantage of quick drug release, which makes it difficult to maintain the synergistic drug ratio for a long time. Herein, we developed a co-delivery system for docetaxel (DTX)—a first-line chemotherapy drug for breast cancer—and salinomycin (SAL)—an anti-BCSCs drug—in rigid nanoparticles constituted of polylactide-co-glycolide/D-alpha-tocopherol polyethylene glycol 1000 succinate (PLGA/TPGS).</p>
</sec>
<sec id="S2002"><title>Methods</title>
<p>Nanoparticles loaded with SAL and DTX at the optimized ratio (NSD) were prepared by the nanoprecipitation method. The characterization, cellular uptake, and cytotoxicity of nanoparticles were investigated in vitro, and the pharmacokinetics, tissue distribution, antitumor and anti-CSCs activity of nanoparticles were evaluated in vivo.</p>
</sec>
<sec id="S2003"><title>Results</title>
<p>We demonstrated that a SAL/DTX molar ratio of 1:1 was synergistic in MCF-7 cells and MCF-7-MS. Moreover, the enhanced internalization of nanoparticles was observed in MCF-7 cells and MCF-7-MS. Furthermore, the cytotoxicity of NSD against both MCF-7 cells and MCF-7-MS was stronger than the cytotoxicity of any single treatment in vitro. Significantly, NSD could prolong the circulation time and maintain the synergistic ratio of SAL to DTX in vivo for 24 h, thus exhibiting superior tumor targeting and anti-tumor activity compared to other treatments.</p>
</sec>
<sec id="S2004"><title>Conclusion</title>
<p>Co-encapsulation of SAL and DTX in PLGA/TPGS nanoparticles could maintain the synergistic ratio of drugs in vivo in a better manner; thus, providing a promising strategy for synergistic inhibition of breast cancer.</p>
</sec>
</div>
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<front><journal-meta><journal-id journal-id-type="nlm-ta">Int J Nanomedicine</journal-id>
<journal-id journal-id-type="iso-abbrev">Int J Nanomedicine</journal-id>
<journal-id journal-id-type="publisher-id">IJN</journal-id>
<journal-id journal-id-type="pmc">intjnano</journal-id>
<journal-title-group><journal-title>International Journal of Nanomedicine</journal-title>
</journal-title-group>
<issn pub-type="ppub">1176-9114</issn>
<issn pub-type="epub">1178-2013</issn>
<publisher><publisher-name>Dove</publisher-name>
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<article-meta><article-id pub-id-type="pmid">32063706</article-id>
<article-id pub-id-type="pmc">6884979</article-id>
<article-id pub-id-type="publisher-id">230376</article-id>
<article-id pub-id-type="doi">10.2147/IJN.S230376</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Original Research</subject>
</subj-group>
</article-categories>
<title-group><article-title>Co-Delivery of Docetaxel and Salinomycin to Target Both Breast Cancer Cells and Stem Cells by PLGA/TPGS Nanoparticles</article-title>
<alt-title alt-title-type="running-authors">Gao et al</alt-title>
<alt-title alt-title-type="running-title">Gao et al</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Gao</surname>
<given-names>Jie</given-names>
</name>
<xref ref-type="corresp" rid="AN0001"></xref>
<xref ref-type="aff" rid="AFF0001">1</xref>
<xref ref-type="aff" rid="AFF0002">2</xref>
<xref ref-type="author-notes" rid="FT0001"></xref>
</contrib>
<contrib contrib-type="author" equal-contrib="yes"><contrib-id contrib-id-type="orcid" authenticated="false">http://orcid.org/0000-0003-0369-1786</contrib-id>
<name><surname>Liu</surname>
<given-names>Junjie</given-names>
</name>
<xref ref-type="aff" rid="AFF0001">1</xref>
<xref ref-type="aff" rid="AFF0003">3</xref>
<xref ref-type="author-notes" rid="FT0001"></xref>
</contrib>
<contrib contrib-type="author" equal-contrib="yes"><name><surname>Xie</surname>
<given-names>Fangyuan</given-names>
</name>
<xref ref-type="aff" rid="AFF0004">4</xref>
<xref ref-type="author-notes" rid="FT0001"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lu</surname>
<given-names>Ying</given-names>
</name>
<xref ref-type="aff" rid="AFF0003">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Yin</surname>
<given-names>Chuan</given-names>
</name>
<xref ref-type="aff" rid="AFF0005">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Shen</surname>
<given-names>Xian</given-names>
</name>
<xref ref-type="aff" rid="AFF0001">1</xref>
</contrib>
<aff id="AFF0001"><label>1</label>
<institution>Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University</institution>
,<addr-line>Zhejiang</addr-line>
,<country>People’s Republic of China</country>
</aff>
<aff id="AFF0002"><label>2</label>
<institution>Scientific Research Center, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University</institution>
,<addr-line>Zhejiang</addr-line>
,<country>People’s Republic of China</country>
</aff>
<aff id="AFF0003"><label>3</label>
<institution>Department of Pharmaceutical Sciences, Second Military Medical University</institution>
,<addr-line>Shanghai</addr-line>
,<country>People’s Republic of China</country>
</aff>
<aff id="AFF0004"><label>4</label>
<institution>Department of Pharmacy, Shanghai Eastern Hepatobiliary Surgery Hospital</institution>
,<addr-line>Shanghai</addr-line>
,<country>People’s Republic of China</country>
</aff>
<aff id="AFF0005"><label>5</label>
<institution>Department of Gastroenterology, Changzheng Hospital, Second Military Medical University</institution>
,<addr-line>Shanghai</addr-line>
,<country>People’s Republic of China</country>
</aff>
</contrib-group>
<author-notes><corresp id="AN0001">Correspondence: Jie Gao; Xian Shen <institution>Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University</institution>
, <addr-line>109 Xueyuan W Road, Lucheng</addr-line>
, <addr-line>Wenzhou</addr-line>
, <addr-line>Zhejiang</addr-line>
<addr-line>325000</addr-line>
, <country>People’s Republic of China</country>
<phone>Tel +86-0577-88816381; 86-0577-88002709</phone>
<fax>Fax +86-0577-88816381</fax>
Email gaojiehighclea@163.com; shenxian1963@sina.com</corresp>
<fn id="FT0001"><label>*</label>
<p>These authors contributed equally to this work</p>
</fn>
</author-notes>
<pub-date pub-type="epub"><day>26</day>
<month>11</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="collection"><year>2019</year>
</pub-date>
<volume>14</volume>
<fpage>9199</fpage>
<lpage>9216</lpage>
<history><date date-type="received"><day>10</day>
<month>9</month>
<year>2019</year>
</date>
<date date-type="accepted"><day>13</day>
<month>11</month>
<year>2019</year>
</date>
</history>
<permissions><copyright-statement>© 2019 Gao et al.</copyright-statement>
<copyright-year>2019</copyright-year>
<copyright-holder>Gao et al.</copyright-holder>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/"><license-p>This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at <ext-link ext-link-type="uri" xlink:href="https://www.dovepress.com/terms.php">https://www.dovepress.com/terms.php</ext-link>
and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/">http://creativecommons.org/licenses/by-nc/3.0/</ext-link>
). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (<ext-link ext-link-type="uri" xlink:href="https://www.dovepress.com/terms.php">https://www.dovepress.com/terms.php</ext-link>
).</license-p>
</license>
</permissions>
<abstract><sec id="S2001"><title>Purpose</title>
<p>Conventional chemotherapy is hampered by the presence of breast cancer stem cells (BCSCs). It is crucial to eradicating both the bulky breast cancer cells and BCSCs, using a combination of conventional chemotherapy and anti-CSCs drugs. However, the synergistic ratio of drug combinations cannot be easily maintained in vivo. In our previous studies, we demonstrated that the simultaneous delivery of two drugs via nanoliposomes could maintain the synergistic drug ratio for 12 h in vivo. However, nanoliposomes have the disadvantage of quick drug release, which makes it difficult to maintain the synergistic drug ratio for a long time. Herein, we developed a co-delivery system for docetaxel (DTX)—a first-line chemotherapy drug for breast cancer—and salinomycin (SAL)—an anti-BCSCs drug—in rigid nanoparticles constituted of polylactide-co-glycolide/D-alpha-tocopherol polyethylene glycol 1000 succinate (PLGA/TPGS).</p>
</sec>
<sec id="S2002"><title>Methods</title>
<p>Nanoparticles loaded with SAL and DTX at the optimized ratio (NSD) were prepared by the nanoprecipitation method. The characterization, cellular uptake, and cytotoxicity of nanoparticles were investigated in vitro, and the pharmacokinetics, tissue distribution, antitumor and anti-CSCs activity of nanoparticles were evaluated in vivo.</p>
</sec>
<sec id="S2003"><title>Results</title>
<p>We demonstrated that a SAL/DTX molar ratio of 1:1 was synergistic in MCF-7 cells and MCF-7-MS. Moreover, the enhanced internalization of nanoparticles was observed in MCF-7 cells and MCF-7-MS. Furthermore, the cytotoxicity of NSD against both MCF-7 cells and MCF-7-MS was stronger than the cytotoxicity of any single treatment in vitro. Significantly, NSD could prolong the circulation time and maintain the synergistic ratio of SAL to DTX in vivo for 24 h, thus exhibiting superior tumor targeting and anti-tumor activity compared to other treatments.</p>
</sec>
<sec id="S2004"><title>Conclusion</title>
<p>Co-encapsulation of SAL and DTX in PLGA/TPGS nanoparticles could maintain the synergistic ratio of drugs in vivo in a better manner; thus, providing a promising strategy for synergistic inhibition of breast cancer.</p>
</sec>
</abstract>
<kwd-group kwd-group-type="author"><title>Keywords</title>
<kwd>combined therapy</kwd>
<kwd>breast cancer stem cells</kwd>
<kwd>docetaxel</kwd>
<kwd>salinomycin</kwd>
<kwd>nanoparticles</kwd>
</kwd-group>
<counts><fig-count count="9"></fig-count>
<table-count count="6"></table-count>
<ref-count count="49"></ref-count>
<page-count count="18"></page-count>
</counts>
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