Mesenchymal stromal cells uptake and release paclitaxel without reducing its anticancer activity

Anticancer Agents Med Chem. 2015;15(3):400-5. doi: 10.2174/1871520614666140618113441.

Abstract

To improve the drug delivery efficiency on target cells, many strategies have been developed including Mesenchymal Stromal Cells (MSCs) approaches. In a previous study, we found that bone-marrow-derived MSCs (BM-MSCs) were able to incorporate and release the anti-tumor and anti-angiogenic drug, Paclitaxel (PTX). In this study, we evaluated the stability of PTX in standard cell culture conditions by analyzing the metabolites produced by MSCs after their incorporation of the drug. We are able to show that MSCs do not release either 3-OH-PTX or 6-OH-PTX metabolites (having a lower anticancer activity) but release an active PTX molecule together with the isomer 7-Epitaxol, is known to maintain the whole biological activity. This confirms that the simple procedure of MSCs priming with a drug (without any genetic cell manipulation), in our case PTX, does not modify the activity of the molecule and provides a new biological-device to carry and deliver PTX in tumor sites, by contributing to improve drug efficacy and target selectivity in cancer therapy.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacokinetics*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Chromatography, High Pressure Liquid
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Paclitaxel / chemistry
  • Paclitaxel / metabolism
  • Paclitaxel / pharmacokinetics*
  • Structure-Activity Relationship
  • Tandem Mass Spectrometry

Substances

  • Antineoplastic Agents
  • Paclitaxel