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

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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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