Nanobody-albumin nanoparticles (NANAPs) for the delivery of a multikinase inhibitor 17864 to EGFR overexpressing tumor cells

Isil Altintas, Raimond Heukers, Roy van der Meel, Marie Lacombe, Maryam Amidi, Paul M.P. van Bergen En Henegouwen, Wim E. Hennink, Raymond M. Schiffelers, Robbert J. Kok

Research output: Contribution to journalArticleAcademicpeer-review

58 Citations (Scopus)

Abstract

A novel, EGFR-targeted nanomedicine has been developed in the current study. Glutaraldehyde crosslinked albumin nanoparticles with a size of approximately 100nm were loaded with the multikinase inhibitor 17864-L(x)-a platinum-bound sunitinib analogue-which couples the drug to methionine residues of albumin and is released in a reductive environment. Albumin nanoparticles were surface-coated with bifunctional polyethylene glycol 3500 (PEG) and a nanobody-the single variable domain of an antibody-(Ega1) against the epidermal growth factor receptor (EGFR). EGa1-PEG functionalized nanoparticles showed a 40-fold higher binding to EGFR-positive 14C squamous head and neck cancer cells in comparison to PEGylated nanoparticles. 17864-L(x) loaded EGa1-PEG nanoparticles were internalized by clathrin-mediated endocytosis and ultimately digested in lysosomes. The intracellular routing of EGa1 targeted nanoparticles leads to a successful release of the kinase inhibitor in the cell and inhibition of proliferation whereas the non-targeted formulations had no antiproliferative effects on 14C cells. The drug loaded targeted nanoparticles were as effective as the free drug in vitro. These results demonstrate that multikinase inhibitor loaded nanoparticles are interesting nanomedicines for the treatment of EGFR-positive cancers.

Original languageEnglish
Pages (from-to)110-118
Number of pages9
JournalJournal of Controlled Release
Volume165
Issue number2
DOIs
Publication statusPublished - 28 Jan 2013
Externally publishedYes

Keywords

  • Antibodies, Immobilized/immunology
  • Cell Line, Tumor
  • Cell Proliferation/drug effects
  • Drug Carriers/chemistry
  • Drug Delivery Systems
  • ErbB Receptors/immunology
  • Head and Neck Neoplasms/drug therapy
  • Humans
  • Nanoparticles/chemistry
  • Protein Kinase Inhibitors/administration & dosage
  • Serum Albumin/chemistry

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