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Biomaterials. 2014 Jan;35(1):601-10. doi: 10.1016/j.biomaterials.2013.10.001. Epub 2013 Oct 16.

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

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1
Cell Biology, Department of Biology, Science Faculty, Utrecht University, 3584 CH Utrecht, The Netherlands.

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.

KEYWORDS:

Albumin nanoparticles; Intracellular delivery; Met; Nanobody; Receptor down regulation; VHH

[Indexed for MEDLINE]

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