Endostatin genetically engineered placental mesenchymal stromal cells carrying mesoporous silica nanoparticles for combined chemo-and antiangiogenic therapy Articles uri icon

authors

  • DE LA TORRE, PAZ
  • PARIS, JUAN L.
  • FERNANDEZ DE LA TORRE, MIGUEL
  • VALLET REGI, MARIA
  • FLORES, ANA I.

publication date

  • February 2021

start page

  • 1

end page

  • 15

issue

  • 2(244)

volume

  • 13

International Standard Serial Number (ISSN)

  • 1999-4923

abstract

  • Combination therapies constitute a powerful tool for cancer treatment. By combining
    drugs with different mechanisms of action, the limitations of each individual agent can be overcome,
    while increasing therapeutic benefit. Here, we propose employing tumor-migrating decidua-derived
    mesenchymal stromal cells as therapeutic agents combining antiangiogenic therapy and chemother apy. First, a plasmid encoding the antiangiogenic protein endostatin was transfected into these cells
    by nucleofection, confirming its expression by ELISA and its biological effect in an ex ovo chick
    embryo model. Second, doxorubicin-loaded mesoporous silica nanoparticles were introduced into
    the cells, which would act as vehicles for the drug being released. The effect of the drug was evalu ated in a coculture in vitro model with mammary cancer cells. Third, the combination of endostatin
    transfection and doxorubicin-nanoparticle loading was carried out with the decidua mesenchymal
    stromal cells. This final cell platform was shown to retain its tumor-migration capacity in vitro, and
    the combined in vitro therapeutic efficacy was confirmed through a 3D spheroid coculture model
    using both cancer and endothelial cells. The results presented here show great potential for the
    development of combination therapies based on genetically-engineered cells that can simultaneously
    act as cellular vehicles for drug-loaded nanoparticles.

subjects

  • Biology and Biomedicine

keywords

  • mesenchymal stromal cells; mesoporous silica nanoparticles; combination therapy; antiangiogenic therapy