Inhibition of colorectal cancer-associated fibroblasts by lipid nanocapsules loaded with acriflavine or paclitaxel.

Fourniols, Thibaut;Bastien, Estelle;Canevat, Alizée;Feron, Olivier;Préat, Véronique
(2020) International Journal of Pharmaceutics — Vol. 584, p. 119337 (2020)

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Authors
  • Fourniols, ThibautUCLouvain
    Author
  • Bastien, Estelle
    Author
  • Canevat, Alizée
    Author
  • Author
  • Préat, VéroniqueUCLouvain
    Author
Abstract
Crosstalk between cancer-associated fibroblasts (CAFs) and colorectal cancer cells promotes tumor growth and contributes to chemoresistance. In this study, we assessed the sensitivity of a primary CAF cell line, CT5.3hTERT, to standard-of-care and alternative cytotoxic treatments. Paclitaxel (PTX) and acriflavine (ACF) were identified as the most promising molecules to inhibit CAF development. To allow the translational use of both drugs, we developed lipid nanocapsule (LNC) formulations for PTX and ACF. Finally, we mixed CAFs and tumor cell lines in a cocultured spheroid, and the effect of both drugs was investigated by histological analyses. We demonstrated CAF inhibition by LNC-ACF and whole tumor inhibition by LNC-PTX. Altogether, we proposed a new strategy to reduce CAF populations in the colorectal microenvironment that should be tested in vivo.
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Citations

Fourniols, T., Bastien, E., Canevat, A., Feron, O., & Préat, V. (2020). Inhibition of colorectal cancer-associated fibroblasts by lipid nanocapsules loaded with acriflavine or paclitaxel. International Journal of Pharmaceutics, 584, 119337. https://doi.org/10.1016/j.ijpharm.2020.119337 (Original work published 2020)