title: Engineering nanocages with polyglutamate domains for coupling to hydroxyapatite biomaterials and allograft bone.
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.
authors: Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors: Bonnie K
authors: BK
authors: Culpepper
authors: David S
authors: DS
authors: Morris
authors: Peter E
authors: PE
authors: Prevelige
authors: Susan L
authors: SL
authors: Bellis
mesh_terms: D017100:Bacteriophage P22 / Q000378:metabolism; D001672:Biocompatible Materials / Q000737:chemistry*; D036022:Capsid Proteins / Q000737:chemistry* / Q000235:genetics; D016503:Drug Delivery Systems / Q000379:methods*; D017886:Durapatite / Q000737:chemistry*; D016297:Mutagenesis, Site-Directed; D053758:Nanoparticles / Q000737:chemistry*; D049329:Nanostructures / Q000737:chemistry*; D011099:Polyglutamic Acid / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D036022:Capsid Proteins; D011099:Polyglutamic Acid; D017886:Durapatite