Delivery of siRNA into breast cancer cells via phage fusion protein-targeted liposomes

• DOI: 10.1016/j.nano.2010.10.004
• Publication Date: 2010-11-03T08:15:47Z
• Authors: Deepa Bedi; Tiziana Musacchio; Olusegun A. Fagbohun; James W. Gillespie; Patricia Deinnoce...; R. Curtis Bird; Lonnie Bookbinder; Vladimir P. Torch...; Valery A. Petrenko
• Keywords: 0301 basic medicine; Transcription, Genetic; Static Electricity; Gene Transfer Techniques; RNA-Binding Proteins; Breast Neoplasms; 3. Good health; DNA-Binding Proteins; Repressor Proteins; Protein Transport; 03 medical and health sciences; Organ Specificity; Cell Line, Tumor; Liposomes; Humans; Bacteriophages; Female; Gene Silencing; Particle Size; RNA, Small Interfering; Oligopeptides; Viral Fusion Proteins; Transcription Factors

Efficacy of siRNAs as potential anticancer therapeutics can be increased by their targeted delivery into cancer cells via tumor-specific ligands. Phage display offers a unique approach to identify highly specific and selective ligands that can deliver nanocarriers to the site of disease. In this study, we proved a novel approach for intracellular delivery of siRNAs into breast cancer cells through their encapsulation into liposomes targeted to the tumor cells with preselected intact phage proteins. The targeted siRNA liposomes were obtained by a fusion of two parental liposomes containing spontaneously inserted siRNA and fusion phage proteins. The presence of pVIII coat protein fused to a MCF-7 cell-targeting peptide DMPGTVLP in the liposomes was confirmed by Western blotting. The novel phage-targeted siRNA-nanopharmaceuticals demonstrate significant down-regulation of PRDM14 gene expression and PRDM14 protein synthesis in the target MCF-7 cells. This approach offers the potential for development of new anticancer siRNA-based targeted nanomedicines.In this study, the authors report a novel approach for targeted intracellular delivery of siRNAs into breast cancer cells through encapsulation into liposomes targeted to the tumor cells with preselected intact phage proteins.