Journal article Open Access

Metabolomics facilitates the discrimination of the specific anti-cancer effects of free- and polymer-conjugated doxorubicin in breast cancer models

Armiñán, Ana; Palomino-Schätzlein, Martina; Deladriere, Coralie; Arroyo-Crespo, Juan J.; Vicente-Ruiz,Sonia; Vicent, María Jesús; Pineda-Lucena, Antonio


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  <identifier identifierType="URL">https://zenodo.org/record/1175906</identifier>
  <creators>
    <creator>
      <creatorName>Armiñán, Ana</creatorName>
      <givenName>Ana</givenName>
      <familyName>Armiñán</familyName>
      <affiliation>Polymer Therapeutics Laboratory, Centro de Investigación Príncipe Felipe, Valencia, Spain.</affiliation>
    </creator>
    <creator>
      <creatorName>Palomino-Schätzlein, Martina</creatorName>
      <givenName>Martina</givenName>
      <familyName>Palomino-Schätzlein</familyName>
      <affiliation>Joint Research Unit in Clinical Metabolomics, Centro de Investigación Príncipe Felipe / Instituto de Investigación Sanitaria La Fe, Valencia, Spain.</affiliation>
    </creator>
    <creator>
      <creatorName>Deladriere, Coralie</creatorName>
      <givenName>Coralie</givenName>
      <familyName>Deladriere</familyName>
      <affiliation>Polymer Therapeutics Laboratory, Centro de Investigación Príncipe Felipe, Valencia, Spain</affiliation>
    </creator>
    <creator>
      <creatorName>Arroyo-Crespo, Juan J.</creatorName>
      <givenName>Juan J.</givenName>
      <familyName>Arroyo-Crespo</familyName>
      <affiliation>Polymer Therapeutics Laboratory, Centro de Investigación Príncipe Felipe, Valencia, Spain</affiliation>
    </creator>
    <creator>
      <creatorName>Vicente-Ruiz,Sonia</creatorName>
      <givenName>Sonia</givenName>
      <familyName>Vicente-Ruiz</familyName>
      <affiliation>Polymer Therapeutics Laboratory, Centro de Investigación Príncipe Felipe, Valencia, Spain</affiliation>
    </creator>
    <creator>
      <creatorName>Vicent, María Jesús</creatorName>
      <givenName>María Jesús</givenName>
      <familyName>Vicent</familyName>
      <affiliation>Polymer Therapeutics Laboratory, Centro de Investigación Príncipe Felipe, Valencia, Spain</affiliation>
    </creator>
    <creator>
      <creatorName>Pineda-Lucena, Antonio</creatorName>
      <givenName>Antonio</givenName>
      <familyName>Pineda-Lucena</familyName>
      <affiliation>de Investigación Sanitaria La Fe, Valencia, Spain. / Drug Discovery Unit, Instituto de Investigación Sanitaria La Fe, Valencia, Spain.</affiliation>
    </creator>
  </creators>
  <titles>
    <title>Metabolomics facilitates the discrimination of the specific anti-cancer effects of free- and polymer-conjugated doxorubicin in breast cancer models</title>
  </titles>
  <publisher>Zenodo</publisher>
  <publicationYear>2018</publicationYear>
  <subjects>
    <subject>metabolomics</subject>
    <subject>NMR</subject>
    <subject>nanomedicine</subject>
    <subject>polymer therapeutics</subject>
    <subject>breast cancer</subject>
  </subjects>
  <dates>
    <date dateType="Issued">2018-02-08</date>
  </dates>
  <resourceType resourceTypeGeneral="Text">Journal article</resourceType>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://zenodo.org/record/1175906</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.1016/j.biomaterials.2018.02.015</relatedIdentifier>
  </relatedIdentifiers>
  <rightsList>
    <rights rightsURI="https://creativecommons.org/licenses/by/4.0/legalcode">Creative Commons Attribution 4.0 International</rights>
    <rights rightsURI="info:eu-repo/semantics/openAccess">Open Access</rights>
  </rightsList>
  <descriptions>
    <description descriptionType="Abstract">&lt;p&gt;Metabolomics is becoming a relevant tool for understanding the molecular mechanisms&lt;br&gt;
involved in the response to new drug delivery systems. The applicability of this experimental&lt;br&gt;
approach to cell cultures and animal models makes metabolomics a useful tool for establishing&lt;br&gt;
direct connections between in vitro and in vivo data, thus providing a reliable platform for the&lt;br&gt;
characterization of chemotherapeutic agents. Herein, we used metabolomic profiles based on&lt;br&gt;
nuclear magnetic resonance (NMR) spectroscopy to evaluate the biochemical pathways involved in&lt;br&gt;
the response to a chemotherapeutic anthracycline drug (Doxorubicin, Dox) and an N-(2-&lt;br&gt;
hydroxypropyl) methacrylamide (HPMA) copolymer-conjugated form (HPMA-Dox) in an in vitro&lt;br&gt;
cell culture model and an in vivo orthotopic breast cancer model. We also used protein expression&lt;br&gt;
and flow cytometry studies to obtain a better coverage of the biochemical alterations associated&lt;br&gt;
with the administration of these compounds. The overall analysis revealed that polymer conjugation&lt;br&gt;
leads to increased apoptosis, reduced glycolysis, and reduced levels of phospholipids when&lt;br&gt;
compared to the free chemotherapeutic drug. Our results represent a first step in the application of&lt;br&gt;
integrated in vitro and in vivo metabolomic studies to the evaluation of drug delivery systems.&lt;/p&gt;</description>
  </descriptions>
  <fundingReferences>
    <fundingReference>
      <funderName>European Commission</funderName>
      <funderIdentifier funderIdentifierType="Crossref Funder ID">10.13039/501100000780</funderIdentifier>
      <awardNumber awardURI="info:eu-repo/grantAgreement/EC/H2020/648831/">648831</awardNumber>
      <awardTitle>Towards the design of Personalised Polymer-based Combination Nanomedicines for Advanced Stage Breast Cancer Patients</awardTitle>
    </fundingReference>
  </fundingReferences>
</resource>
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