Characterisation of THP-1 macrophages as an in vitro model for CD44-targeted therapies

摘要

CD44 is the major cell surface receptor of hyaluronic acid (HA) and mediates the response of cells to their microenvironment. Whereas the standard isoform (CD44s) is ubiquitously expressed throughout the body, variant isoforms (CD44v) are aberrantly overexpressed in certain tumours, thus CD44 has become a potential target for cancer chemotherapy. However, CD44 is also one of the most abundantly expressed macrophage receptors, rendering this cellular type a potential competitor for the uptake of targeted nanocarriers in vivo. An in vitro human macrophage model is described herein. This model would allow to evaluate CD44 off-targeting. In particular, we have developed a procedure for the differentiation and activation of THP-1 cells. The CD44 expression of THP-1 macrophages was compared to that of the tumoural cell line HT-29 in terms of amount and isoform composition. The internalisation kinetics of HA nanoparticles was also evaluated.