title: Targeted delivery of siRNA into breast cancer cells via phage fusion proteins.
abstract: Nucleic acids, including antisense oligonucleotides, small interfering RNA (siRNA), aptamers, and rybozymes, emerged as versatile therapeutics due to their ability to interfere in a well-planned manner with the flow of genetic information from DNA to protein. However, a systemic use of NAs is hindered by their instability in physiological liquids and inability of intracellular accumulation in the site of action. We first evaluated the potential of cancer specific phage fusion proteins as targeting ligands that provide encapsulation, protection, and navigation of siRNA to the target cell. The tumor-specific proteins were isolated from phages that were affinity selected from a landscape phage library against target breast cancer cells. It was found that fusion phage coat protein fpVIII displaying cancer-targeting peptides can effectively encapsulate siRNAs and deliver them into the cells leading to specific silencing of the model gene GAPDH. Complexes of siRNA and phage protein form nanoparticles (nanophages), which were characterized by atomic force microscopy and ELISA, and their stability was demonstrated by resistance of encapsulated siRNA to degradation by serum nucleases. The phage protein/siRNA complexes can make a new type of highly selective, stable, active, and physiologically acceptable cancer nanomedicine.
authors.affiliation: Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, Alabama 36849, United States.
authors.forename: Deepa
authors.initials: D
authors.lastname: Bedi
authors.forename: James W
authors.initials: JW
authors.lastname: Gillespie
authors.forename: Vasily A
authors.initials: VA
authors.lastname: Petrenko
authors.forename: Andreas
authors.initials: A
authors.lastname: Ebner
authors.forename: Michael
authors.initials: M
authors.lastname: Leitner
authors.forename: Peter
authors.initials: P
authors.lastname: Hinterdorfer
authors.forename: Valery A
authors.initials: VA
authors.lastname: Petrenko
mesh_terms: D001435:Bacteriophages / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage / Q000737:chemistry; D056945:Hep G2 Cells; D006801:Humans; D018625:Microscopy, Atomic Force; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics / Q000502:physiology; D014764:Viral Proteins / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D034741:RNA, Small Interfering; D014764:Viral Proteins