Development of dual-targeted nano-dandelion based on an oligomeric hyaluronic acid polymer targeting tumor-associated macrophages for combination therapy of non-small cell lung cancer
Identifieur interne : 000493 ( Pmc/Curation ); précédent : 000492; suivant : 000494Development of dual-targeted nano-dandelion based on an oligomeric hyaluronic acid polymer targeting tumor-associated macrophages for combination therapy of non-small cell lung cancer
Auteurs : Bingjie Wang [République populaire de Chine] ; Wei Zhang [République populaire de Chine] ; Xiudi Zhou [République populaire de Chine] ; Mengna Liu [République populaire de Chine] ; Xiaoya Hou [République populaire de Chine] ; Ziting Cheng [République populaire de Chine] ; Daquan Chen [République populaire de Chine]Source :
- Drug Delivery [ 1071-7544 ] ; 2019.
Abstract
In this study, the novel carrier materials were screened to structure targeting nano-micelles (named ‘nano-dandelion’) for synchronous delivery of curcumin (Cur) and baicalin (Bai), which could effectively overcome the tumor resistance. Mannose (Man) was found to bind better to CD206 receptors on the surface of tumor-associated macrophages (TAMs), thereby increasing the number of nano-dandelion engulfed by TAMs. Furthermore, oligomeric hyaluronic acid (oHA) was able to target CD44 receptors, resulting in recruitment of a higher number of nano-dandelion to locate and engulf tumor cells. The disulfide bond (S–S) in 3,3′-dithiodipropionic acid (DA) could be broken by the high concentration of glutathione (GSH) in the tumor microenvironment (TME). Based on this, we selected DA to connect hydrophobic fragments (quercetin, Que) and oHA. A reduction-sensitive amphiphilic carrier material, quercetin–dithiodipropionic acid–oligomeric hyaluronic acid–mannose–ferulic acid (Que–S–S–oHA–Man–FA; QHMF) was fabricated and synthesized by 1H NMR. Next, QHMF self-assembled into nano-dandelion, i.e. encapsulated Cur and Bai in water. Critical experimental conditions in the preparation process of nano-dandelion that could affect its final properties were explored. Nano-dandelion with a small particle size (121.0 ± 15 nm) and good normal distribution (PI = 0.129) could easily enter tumor tissue through vascular barrier. In addition, nano-dandelion with a suitable surface potential (–20.33 ± 4.02 mV) could remain stable for a long duration. Furthermore, good cellular penetration and tumor cytotoxicity of nano-dandelion were demonstrated through
Url:
DOI: 10.1080/10717544.2019.1693707
PubMed: 31777307
PubMed Central: 6896416
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<series><title level="j">Drug Delivery</title>
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<front><div type="abstract" xml:lang="en"><title>Abstract</title>
<p>In this study, the novel carrier materials were screened to structure targeting nano-micelles (named ‘nano-dandelion’) for synchronous delivery of curcumin (Cur) and baicalin (Bai), which could effectively overcome the tumor resistance. Mannose (Man) was found to bind better to CD206 receptors on the surface of tumor-associated macrophages (TAMs), thereby increasing the number of nano-dandelion engulfed by TAMs. Furthermore, oligomeric hyaluronic acid (oHA) was able to target CD44 receptors, resulting in recruitment of a higher number of nano-dandelion to locate and engulf tumor cells. The disulfide bond (S–S) in 3,3′-dithiodipropionic acid (DA) could be broken by the high concentration of glutathione (GSH) in the tumor microenvironment (TME). Based on this, we selected DA to connect hydrophobic fragments (quercetin, Que) and oHA. A reduction-sensitive amphiphilic carrier material, quercetin–dithiodipropionic acid–oligomeric hyaluronic acid–mannose–ferulic acid (Que–S–S–oHA–Man–FA; QHMF) was fabricated and synthesized by <sup>1</sup>
H NMR. Next, QHMF self-assembled into nano-dandelion, i.e. encapsulated Cur and Bai in water. Critical experimental conditions in the preparation process of nano-dandelion that could affect its final properties were explored. Nano-dandelion with a small particle size (121.0 ± 15 nm) and good normal distribution (PI = 0.129) could easily enter tumor tissue through vascular barrier. In addition, nano-dandelion with a suitable surface potential (–20.33 ± 4.02 mV) could remain stable for a long duration. Furthermore, good cellular penetration and tumor cytotoxicity of nano-dandelion were demonstrated through <italic>in vitro</italic>
cellular studies. Finally, effective antitumor activity and reduced side effects were confirmed through <italic>in vivo</italic>
antitumor experiments in A549 tumor-bearing nude mice.</p>
</div>
</front>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Drug Deliv</journal-id>
<journal-id journal-id-type="iso-abbrev">Drug Deliv</journal-id>
<journal-id journal-id-type="publisher-id">IDRD</journal-id>
<journal-id journal-id-type="publisher-id">idrd20</journal-id>
<journal-title-group><journal-title>Drug Delivery</journal-title>
</journal-title-group>
<issn pub-type="ppub">1071-7544</issn>
<issn pub-type="epub">1521-0464</issn>
<publisher><publisher-name>Taylor & Francis</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">31777307</article-id>
<article-id pub-id-type="pmc">6896416</article-id>
<article-id pub-id-type="doi">10.1080/10717544.2019.1693707</article-id>
<article-id pub-id-type="publisher-id">1693707</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Development of dual-targeted nano-dandelion based on an oligomeric hyaluronic acid polymer targeting tumor-associated macrophages for combination therapy of non-small cell lung cancer</article-title>
<alt-title alt-title-type="running-authors">B. Wang et al.</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Wang</surname>
<given-names>Bingjie</given-names>
</name>
<xref ref-type="aff" rid="AF0001"><sup>a</sup>
</xref>
<xref ref-type="author-notes" rid="FN0001"><sup>*</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zhang</surname>
<given-names>Wei</given-names>
</name>
<xref ref-type="aff" rid="AF0002"><sup>b</sup>
</xref>
<xref ref-type="author-notes" rid="FN0001"><sup>*</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zhou</surname>
<given-names>Xiudi</given-names>
</name>
<xref ref-type="aff" rid="AF0001"><sup>a</sup>
</xref>
<xref ref-type="aff" rid="AF0003"><sup>c</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Liu</surname>
<given-names>Mengna</given-names>
</name>
<xref ref-type="aff" rid="AF0001"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hou</surname>
<given-names>Xiaoya</given-names>
</name>
<xref ref-type="aff" rid="AF0001"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Cheng</surname>
<given-names>Ziting</given-names>
</name>
<xref ref-type="aff" rid="AF0001"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-6796-0204</contrib-id>
<name><surname>Chen</surname>
<given-names>Daquan</given-names>
</name>
<xref ref-type="aff" rid="AF0001"><sup>a</sup>
</xref>
<xref ref-type="corresp" rid="AN0001"></xref>
</contrib>
<aff id="AF0001"><label>a</label>
<institution>School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs, Universities of Shandong, Yantai University</institution>
, Yantai,<country>PR China</country>
;</aff>
<aff id="AF0002"><label>b</label>
<institution>Department of Radiotherapy, Affiliated Yantai Yuhuangding Hospital of Qingdao University</institution>
, Yantai,<country>PR China</country>
;</aff>
<aff id="AF0003"><label>c</label>
<institution>Department of Pharmacy, Binzhou People’s Hospital</institution>
, Binzhou,<country>PR China</country>
</aff>
</contrib-group>
<author-notes><fn id="FN0001"><label>*</label>
<p>These authors contributed equally to this work.</p>
</fn>
<corresp id="AN0001"><bold>CONTACT</bold>
Daquan Chen <email>cdq1981@126.com</email>
<institution>School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs, Universities of Shandong, Yantai University</institution>
, Yantai 264005, Shandong, <country>PR China</country>
</corresp>
</author-notes>
<pub-date pub-type="collection"><year>2019</year>
</pub-date>
<pub-date pub-type="epub"><day>28</day>
<month>11</month>
<year>2019</year>
</pub-date>
<volume>26</volume>
<issue>1</issue>
<fpage seq="121">1265</fpage>
<lpage>1279</lpage>
<history><date date-type="received"><day>30</day>
<month>9</month>
<year>2019</year>
</date>
<date date-type="rev-recd"><day>05</day>
<month>11</month>
<year>2019</year>
</date>
<date date-type="accepted"><day>11</day>
<month>11</month>
<year>2019</year>
</date>
</history>
<permissions><copyright-statement>© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.</copyright-statement>
<copyright-year>2019</copyright-year>
<copyright-holder>The Author(s)</copyright-holder>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>
), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
</license>
</permissions>
<self-uri content-type="pdf" xlink:href="IDRD_26_1693707.pdf"></self-uri>
<abstract><title>Abstract</title>
<p>In this study, the novel carrier materials were screened to structure targeting nano-micelles (named ‘nano-dandelion’) for synchronous delivery of curcumin (Cur) and baicalin (Bai), which could effectively overcome the tumor resistance. Mannose (Man) was found to bind better to CD206 receptors on the surface of tumor-associated macrophages (TAMs), thereby increasing the number of nano-dandelion engulfed by TAMs. Furthermore, oligomeric hyaluronic acid (oHA) was able to target CD44 receptors, resulting in recruitment of a higher number of nano-dandelion to locate and engulf tumor cells. The disulfide bond (S–S) in 3,3′-dithiodipropionic acid (DA) could be broken by the high concentration of glutathione (GSH) in the tumor microenvironment (TME). Based on this, we selected DA to connect hydrophobic fragments (quercetin, Que) and oHA. A reduction-sensitive amphiphilic carrier material, quercetin–dithiodipropionic acid–oligomeric hyaluronic acid–mannose–ferulic acid (Que–S–S–oHA–Man–FA; QHMF) was fabricated and synthesized by <sup>1</sup>
H NMR. Next, QHMF self-assembled into nano-dandelion, i.e. encapsulated Cur and Bai in water. Critical experimental conditions in the preparation process of nano-dandelion that could affect its final properties were explored. Nano-dandelion with a small particle size (121.0 ± 15 nm) and good normal distribution (PI = 0.129) could easily enter tumor tissue through vascular barrier. In addition, nano-dandelion with a suitable surface potential (–20.33 ± 4.02 mV) could remain stable for a long duration. Furthermore, good cellular penetration and tumor cytotoxicity of nano-dandelion were demonstrated through <italic>in vitro</italic>
cellular studies. Finally, effective antitumor activity and reduced side effects were confirmed through <italic>in vivo</italic>
antitumor experiments in A549 tumor-bearing nude mice.</p>
</abstract>
<kwd-group kwd-group-type="author"><title>Keywords</title>
<kwd>Combination therapy for non-small cell lung cancer</kwd>
<kwd>curcumin and baicalin co-delivery</kwd>
<kwd>dual-targeted nano-dandelion</kwd>
<kwd>oligomeric hyaluronic acid polymer</kwd>
<kwd>targeting tumor-associated macrophage</kwd>
</kwd-group>
<funding-group><award-group><funding-source><named-content content-type="funder-name">National Natural Science Foundation of China</named-content>
<named-content content-type="funderidentifier">10.13039/501100001809</named-content>
</funding-source>
<award-id>81573614</award-id>
</award-group>
<award-group><funding-source><named-content content-type="funder-name">Taishan Scholar Program</named-content>
</funding-source>
<award-id>qnts20161035</award-id>
</award-group>
<award-group><funding-source><named-content content-type="funder-name">Shandong Provincial Natural Science Foundation for Outstanding Young Scholar</named-content>
</funding-source>
<award-id>ZR2019YQ30</award-id>
</award-group>
<funding-statement>This study was financially supported by the National Natural Science Foundation of China (No. 81573614); Taishan Scholar Program (No. qnts20161035); Shandong Provincial Natural Science Foundation for Outstanding Young Scholar (No. ZR2019YQ30).</funding-statement>
</funding-group>
<counts><fig-count count="11"></fig-count>
<table-count count="1"></table-count>
<page-count count="15"></page-count>
<word-count count="7394"></word-count>
</counts>
</article-meta>
</front>
</pmc>
</record>
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