title: Target-specific copper hybrid T7 phage particles.
abstract: Target-specific nanoparticles have attracted significant attention recently, and have greatly impacted life and physical sciences as new agents for imaging, diagnosis, and therapy, as well as building blocks for the assembly of novel complex materials. While most of these particles are synthesized by chemical conjugation of an affinity reagent to polymer or inorganic nanoparticles, we are promoting the use of phage particles as a carrier to host organic or inorganic functional components, as well as to display the affinity reagent on the phage surface, taking advantage of the fact that some phages host well-established vectors for protein expression. An affinity reagent can be structured in a desired geometry on the surface of phage particles, and more importantly, the number of the affinity reagent molecules per phage particle can be precisely controlled. We previously have reported the use of the T7 phage capsid as a template for synthesizing target-specific metal nanoparticles. In this study herein, we reported the synthesis of nanoparticles using an intact T7 phage as a scaffold from which to extend 415 copies of a peptide that contains a hexahistidine (6His) motif for capture of copper ions and staging the conversion of copper ions to copper metal, and a cyclic Arginine-Glycine-Aspartic Acid (RGD4C) motif for targeting integrin and cancer cells. We demonstrated that the recombinant phage could load copper ions under low bulk copper concentrations without interfering with its target specificity. Further reduction of copper ions to copper metal rendered a very stable copper hybrid T7 phage, which prevents the detachment of copper from phage particles and maintains the phage structural integrity even under harsh conditions. Cancer cells (MCF-7) can selectively uptake copper hybrid T7 phage particles through ligand-mediated transmembrane transportation, whereas normal control cells (MCF-12F) uptake 1000-fold less. We further demonstrated that copper hybrid T7 phage could be endocytosed by cancer cells in culture.
authors.affiliation: Department of Chemistry and Biochemistry, Utah State University, Logan, Utah, USA.
authors.forename: Siva Sai Krishna
authors.initials: SS
authors.lastname: Dasa
authors.forename: Qiaoling
authors.initials: Q
authors.lastname: Jin
authors.forename: Chin-Tu
authors.initials: CT
authors.lastname: Chen
authors.forename: Liaohai
authors.initials: L
authors.lastname: Chen
mesh_terms: D020816:Amino Acid Motifs; D017123:Bacteriophage T7 / Q000737:chemistry*; D045744:Cell Line, Tumor; D003300:Copper / Q000737:chemistry* / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods; D004705:Endocytosis; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*
chemical_list: D003300:Copper