Engineering nanocages with polyglutamate domains for coupling to hydroxyapatite biomaterials and allograft bone

Biomaterials. 2013 Mar;34(10):2455-62. doi: 10.1016/j.biomaterials.2012.12.026. Epub 2013 Jan 11.

Abstract

Hydroxyapatite (HA) is the principal constituent of bone mineral, and synthetic HA is widely used as a biomaterial for bone repair. Previous work has shown that polyglutamate domains bind selectively to HA and that these domains can be utilized to couple bioactive peptides onto many different HA-containing materials. In the current study we have adapted this technology to engineer polyglutamate domains into cargo-loaded nanocage structures derived from the P22 bacteriophage. P22 nanocages have demonstrated significant potential as a drug delivery system due to their stability, large capacity for loading with a diversity of proteins and other types of cargo, and ability to resist degradation by proteases. Site-directed mutagenesis was used to modify the primary coding sequence of the P22 coat protein to incorporate glutamate-rich regions. Relative to wild-type P22, the polyglutamate-modified nanocages (E2-P22) exhibited increased binding to ceramic HA disks, particulate HA and allograft bone. Furthermore, E2-P22 binding was HA selective, as evidenced by negligible binding of the nanocages to non-HA materials including polystyrene, agarose, and polycaprolactone (PCL). Taken together these results establish a new mechanism for the directed coupling of nanocage drug delivery systems to a variety of HA-containing materials commonly used in diverse bone therapies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteriophage P22 / metabolism
  • Biocompatible Materials / chemistry*
  • Capsid Proteins / chemistry*
  • Capsid Proteins / genetics
  • Drug Delivery Systems / methods*
  • Durapatite / chemistry*
  • Mutagenesis, Site-Directed
  • Nanoparticles / chemistry*
  • Nanostructures / chemistry*
  • Polyglutamic Acid / chemistry*

Substances

  • Biocompatible Materials
  • Capsid Proteins
  • Polyglutamic Acid
  • Durapatite