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


BACKGROUND
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.
Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, Alabama, USA.
Deepa
D
Bedi
Tiziana
T
Musacchio
Olusegun A
OA
Fagbohun
James W
JW
Gillespie
Patricia
P
Deinnocentes
R Curtis
RC
Bird
Lonnie
L
Bookbinder
Vladimir P
VP
Torchilin
Valery A
VA
Petrenko
D001435:Bacteriophages / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000821:virology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins; D005260:Female; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D009842:Oligopeptides / Q000378:metabolism*; D009928:Organ Specificity; D010316:Particle Size; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000378:metabolism*; D016601:RNA-Binding Proteins; D012097:Repressor Proteins / Q000378:metabolism; D055672:Static Electricity; D014157:Transcription Factors; D014158:Transcription, Genetic; D014760:Viral Fusion Proteins / Q000378:metabolism*
D004268:DNA-Binding Proteins; D008081:Liposomes; D009842:Oligopeptides; C524724:PRDM14 protein, human; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D014760:Viral Fusion Proteins; C570221:aspartyl-methionyl-prolyl-glycyl-threonyl-valyl-leucyl-proline