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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    <subfield code="c">2018-02-08</subfield>
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    <subfield code="a">&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;</subfield>
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    <subfield code="u">Joint Research Unit in Clinical Metabolomics, Centro de Investigación Príncipe Felipe / Instituto de Investigación Sanitaria La Fe, Valencia, Spain.</subfield>
    <subfield code="a">Palomino-Schätzlein, Martina</subfield>
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    <subfield code="a">Vicent, María Jesús</subfield>
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    <subfield code="u">de Investigación Sanitaria La Fe, Valencia, Spain. / Drug Discovery Unit, Instituto de Investigación Sanitaria La Fe, Valencia, Spain.</subfield>
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    <subfield code="u">Polymer Therapeutics Laboratory, Centro de Investigación Príncipe Felipe, Valencia, Spain.</subfield>
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    <subfield code="a">10.1016/j.biomaterials.2018.02.015</subfield>
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    <subfield code="a">Metabolomics facilitates the discrimination of the specific anti-cancer effects of free- and polymer-conjugated doxorubicin in breast cancer models</subfield>
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    <subfield code="a">Towards the design of Personalised Polymer-based Combination Nanomedicines for Advanced Stage Breast Cancer Patients</subfield>
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