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.

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Human serum albumin (HSA) nanoparticles represent a promising tool for targeted drug delivery to tumor cells. The coupling of the antibody trastuzumab to nanoparticles uses the capability of human epidermal growth factor receptor 2 (HER2)-positive cells to incorporate agents linked to HER2. In our present study, we developed targeted nanoparticles loaded with antisense oligonucleotides (ASOs) against polo-like kinase 1 (Plk1). We evaluated the receptor-mediated uptake into HER2-positive and -negative breast cancer and murine cell lines. We performed quantitative real-time PCR and Western blot analyses to monitor the impact on Plk1 expression in HER2-positive breast cancer cells. Antibody-conjugated nanoparticles showed a specific targeting to HER2-overexpressing cells with cellular uptake by receptor-mediated endocytosis and a release into HER2-positive BT-474 cells. We observed a significant reduction of Plk1 mRNA and protein expression and increased activation of Caspase 3/7. Thus, this is the first report about ASO-loaded HSA nanoparticles, where an impact on gene expression could be observed. The data provide the basis for the further development of carrier systems for Plk1-specific ASOs to reduce off-target effects evoked by systemically administered ASOs and to achieve a better penetration into primary and metastatic target cells. Treatment of tumors using trastuzumab-conjugated ASO-loaded HSA nanoparticles could be a promising approach to reach this goal.

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