Active targeting of tumor cells relies on the use of ligands capable of specifically binding to receptors that are overexpressed on their surface, such as EGFR (epidermal growth factor receptor). Among these ligands, monoclonal antibodies and aptamers are promising tools for the targeted delivery of therapeutic molecules (chemotherapy agents, siRNA, etc.). However, their efficacy depends on their internalization into target cells.
In this study published in Nanoscale, Charlène D’Ancona, Elisabete Cruz Da Silva (ex PhD) and Léa Denechere from the Aptamer group, led by Laurence Choulier of the BIMC team, demonstrated that gefitinib, an EGFR inhibitor that induces massive, non-physiological endocytosis of EGFR (GME) in glioblastoma models, may also promote the endocytosis of EGFR ligands, such as antibodies or aptamers.
The results show that:
- Gefitinib significantly increases the endocytosis of fluorescent antibodies and aptamers targeting EGFR, as confirmed by quantitative bioimaging.
- GME potentiates the efficacy of an antibody-drug conjugate (ADC) and an aptamer-siRNA conjugate (AsiC) in vitro.
These results suggest that gefitinib could optimize the delivery of therapeutic conjugates targeting EGFR.
Although in vivo data indicate that further optimization is needed for clinical application, this study highlights the potential of gefitinib to enhance the efficacy of targeted therapies in glioblastoma cells.
Congratulations to all the authors and contributors from the LBP and and the PIQ QuEst platform, the PCBIS (UAR3286 CNRS), and Biomaterials and Bioengineering (UMR_S 1121 Inserm, EMR CNRS 7003).
Link: Nanoscale (2026) https://doi.org/10.1039/d6nr00420b
