Specific Targeting of HER2 Overexpressing Breast Cancer Cells with Doxorubicin-Loaded Trastuzumab-Modified Human Serum Albumin Nanoparticles

• Published in: Bioconjugate chemistry 2008-12, Vol.19 (12), p.2321-2331
• Main Authors: Anhorn, Marion G, Wagner, Sylvia, Kreuter, Jörg, Langer, Klaus, von Briesen, Hagen
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Biochemistry; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Line, Tumor; Cell Survival - drug effects; Chemotherapy; Cytostatic Agents - metabolism; Cytostatic Agents - pharmacology; Doxorubicin - metabolism; Doxorubicin - pharmacology; Drug Carriers - metabolism; Gene Expression Regulation, Neoplastic; Humans; Intracellular Space - metabolism; Nanoparticles; Proteins; Receptor, ErbB-2 - metabolism; Serum Albumin; Studies; Substrate Specificity; Trastuzumab; Tumors
• ISSN: 1043-1802; 1520-4812
• DOI: 10.1021/bc8002452

Specific targeting of tumor cells to achieve higher drug levels in tumor tissue and to overcome cardiotoxic and other secondary effects is the major goal in cancer therapy. With trastuzumab as a humanized monoclonal antibody binding, the HER2 receptor specific targeting is possible. In the present study, target-oriented nanoparticles based on biodegradable human serum albumin (HSA) loaded with cytostatic drug doxorubicin were developed. The surface of the nanoparticles was modified by covalent attachment of trastuzumab. HER2 overexpressing breast cancer cells showed a good cellular binding and uptake of these nanoparticles. The specific transport of the cytostatic drug doxorubicin with this nanoparticulate formulation into the HER2 overexpressing breast cancer cells, their release, and biological activity was demonstrated. The results indicate that these cell-type specific drug-loaded nanoparticles could achieve an improvement in cancer therapy. To our knowledge, this is the first study demonstrating a specific trastuzumab-based targeting of HER2 overexpressing breast cancer cells with doxorubicin-loaded nanoparticles.