Targeting hepatocyte growth factor receptor (Met) positive tumor cells using internalizing nanobody-decorated albumin nanoparticles

R. Heukers, I. Altintas, S. Raghoenath, E. De Zan, R. Pepermans, R.C. Roovers, R. Haselberg, W.E. Hennink, R.M. Schiffelers, R.J. Kok, P.M.P. van Bergen en Henegouwen

Research output: Contribution to JournalArticle

Abstract

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.
Original languageEnglish
Pages (from-to)601-610
JournalBiomaterials
Volume35
DOIs
Publication statusPublished - 2014

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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