Uptake of plasmid-loaded nanoparticles in breast cancer cells and effect on Plk1 expression

• Published in: Journal of drug targeting Vol. 17; no. 8; pp. 627 - 637
• Main Authors: Steinhauser, Isabel, Langer, Klaus, Strebhardt, Klaus, Spänkuch, Birgit
• Format: Journal Article
• Language: English
• Published: England Informa UK Ltd 01.09.2009; Taylor & Francis
• Subjects: Animals; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal, Humanized; Antineoplastic Agents - administration & dosage; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Cell Cycle Proteins - genetics; Cell Line, Tumor; Drug Carriers - chemistry; Drug Delivery Systems; expression plasmids; Gene Expression Regulation, Neoplastic - drug effects; HSA nanoparticles; Humans; Mice; Nanoparticles; Plasmids - administration & dosage; Polo-Like Kinase 1; polo-like kinase 1 (Plk1); Protein Serine-Threonine Kinases - genetics; Proto-Oncogene Proteins - genetics; Receptor, ErbB-2 - metabolism; RNA Interference; RNA, Small Interfering - administration & dosage; Serum Albumin - chemistry; Trastuzumab
• ISSN: 1061-186X; 1029-2330
• DOI: 10.1080/10611860903118823

The development of nucleic acid-based drugs for cancer therapeutic application has shown promising results in the past. However the delivery of these drugs to target cells is one problem which remains to be resolved. Nanoparticles have been described as promising strategies to deliver drugs into target cells. Human serum albumin (HSA) nanoparticles conjugated to trastuzumab for a cell type-specific targeting of human epidermal growth factor receptor 2 (HER2)-overexpressing cells were developed with incorporated expression plasmids for small hairpin RNAs (shRNAs) targeting polo-like kinase 1 (Plk1). Plk1 is a promising target for such an approach because it is overexpressed in all known cancer types and is a negative prognostic factor. Receptor-mediated uptake of the trastuzumab-modified nanoparticles into HER2-positive cells could be observed leading to reduced Plk1 expression. Taken together, HSA nanoparticles represent promising tools to deliver expression plasmids for shRNAs into target cells and should be further evaluated with regard to a therapeutic application of RNA interference in cancer therapy.