title: Highly specific HER2-mediated cellular uptake of antibody-modified nanoparticles in tumour cells.
abstract: Nanoparticles represent useful drug delivery systems for the specific transport of drugs to tumour cells. In the present study biodegradable nanoparticles based on gelatin and human serum albumin (HSA) were developed. The surface of the nanoparticles was modified by covalent attachment of the biotin-binding protein NeutrAvidin enabling the binding of biotinylated drug targeting ligands by avidin-biotin-complex formation. Using the HER2 receptor specific antibody trastuzumab (Herceptin) conjugated to the surface of these nanoparticles, a specific targeting to HER2-overexpressing cells could be shown. Attachment of the antibody-conjugated nanoparticles to the surface of HER2-overexpressing cells was time and dose dependent. Confocal laser scanning microscopy demonstrated an effective internalisation of the nanoparticles by HER2-overexpressing cells via receptor-mediated endocytosis. The results indicate that nanoparticles conjugated with an antibody against a specific tumour antigen holds promise, as selective drug delivery systems for the treatment of tumours expressing a specific tumour antigen. To our knowledge, this is the first study that demonstrates the effective and specific targeting of protein-based nanoparticles as drug delivery systems.
authors.affiliation: Institute for Pharmaceutical Technology, Biocenter of Johann Wolfgang Goethe-University, Marie-Curie-Strasse 9, D-60439 Frankfurt, Germany.
authors.forename: Heidrun
authors.initials: H
authors.lastname: Wartlick
authors.forename: Kerstin
authors.initials: K
authors.lastname: Michaelis
authors.forename: Sabine
authors.initials: S
authors.lastname: Balthasar
authors.forename: Klaus
authors.initials: K
authors.lastname: Strebhardt
authors.forename: Jörg
authors.initials: J
authors.lastname: Kreuter
authors.forename: Klaus
authors.initials: K
authors.lastname: Langer
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000918:Antibody Specificity; D001665:Binding Sites; D001710:Biotin / Q000737:chemistry; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D005079:Excipients; D005434:Flow Cytometry; D005780:Gelatin; D018734:Genes, erbB-2 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology*; D018613:Microscopy, Confocal; D008863:Microspheres; D009369:Neoplasms / Q000378:metabolism*; D012709:Serum Albumin; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D005079:Excipients; D000922:Immunotoxins; D012709:Serum Albumin; D001710:Biotin; D005780:Gelatin; D000068878:Trastuzumab