The hepatocyte growth factor receptor (HGFR, c-Met or Met) is a receptor tyrosine kinase that is involved in embryogenesis, tissue regeneration and wound healing. Abnormal activation of this proto-oncogene product is implicated in the development, progression and metastasis of many cancers. Current therapies directed against Met, such as ligand- or, dimerization-blocking antibodies or kinase inhibitors, reduce tumor growth but hardly eradicate the tumor. In order to improve anti-Met therapy, we have designed a drug delivery system consisting of crosslinked albumin nanoparticles decorated with newly selected anti-Met nanobodies (anti-Met-NANAPs). The anti-Met NANAPs bound specifically to and were specifically taken up by Met-expressing cells and transported to lysosomes for degradation. Treatment of tumor cells with anti-Met NANAPs also resulted in downregulation of the total Met protein. This study shows that anti-Met NANAPs offer a potential system for lysosomal delivery of drugs into Met-positive tumor cells. © 2013 Elsevier Ltd.
|Publication status||Published - 2014|
Heukers, R., Altintas, I., Raghoenath, S., De Zan, E., Pepermans, R., Roovers, R. C., ... van Bergen en Henegouwen, P. M. P. (2014). Targeting hepatocyte growth factor receptor (Met) positive tumor cells using internalizing nanobody-decorated albumin nanoparticles. Biomaterials, 35, 601-610. https://doi.org/10.1016/j.biomaterials.2013.10.001