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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{
  "DOI": "10.1016/j.biomaterials.2018.02.015", 
  "author": [
    {
      "family": "Armi\u00f1\u00e1n, Ana"
    }, 
    {
      "family": "Palomino-Sch\u00e4tzlein, Martina"
    }, 
    {
      "family": "Deladriere, Coralie"
    }, 
    {
      "family": "Arroyo-Crespo, Juan J."
    }, 
    {
      "family": "Vicente-Ruiz,Sonia"
    }, 
    {
      "family": "Vicent, Mar\u00eda Jes\u00fas"
    }, 
    {
      "family": "Pineda-Lucena, Antonio"
    }
  ], 
  "issued": {
    "date-parts": [
      [
        2018, 
        2, 
        8
      ]
    ]
  }, 
  "abstract": "<p>Metabolomics is becoming a relevant tool for understanding the molecular mechanisms<br>\ninvolved in the response to new drug delivery systems. The applicability of this experimental<br>\napproach to cell cultures and animal models makes metabolomics a useful tool for establishing<br>\ndirect connections between in vitro and in vivo data, thus providing a reliable platform for the<br>\ncharacterization of chemotherapeutic agents. Herein, we used metabolomic profiles based on<br>\nnuclear magnetic resonance (NMR) spectroscopy to evaluate the biochemical pathways involved in<br>\nthe response to a chemotherapeutic anthracycline drug (Doxorubicin, Dox) and an N-(2-<br>\nhydroxypropyl) methacrylamide (HPMA) copolymer-conjugated form (HPMA-Dox) in an in vitro<br>\ncell culture model and an in vivo orthotopic breast cancer model. We also used protein expression<br>\nand flow cytometry studies to obtain a better coverage of the biochemical alterations associated<br>\nwith the administration of these compounds. The overall analysis revealed that polymer conjugation<br>\nleads to increased apoptosis, reduced glycolysis, and reduced levels of phospholipids when<br>\ncompared to the free chemotherapeutic drug. Our results represent a first step in the application of<br>\nintegrated in vitro and in vivo metabolomic studies to the evaluation of drug delivery systems.</p>", 
  "title": "Metabolomics facilitates the discrimination of the specific anti-cancer effects of free- and polymer-conjugated doxorubicin in breast cancer models", 
  "type": "article-journal", 
  "id": "1175906"
}
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