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.