Cell targeting with hybrid Qβ virus-like particles displaying epidermal growth factor

Abstract

Structurally uniform protein nanoparticles derived from the self-assembly of viral capsid proteins are attractive platforms for the multivalent display of cell-targeting motifs for use in nanomedicine. Virus-based nanoparticles are of particular interest because the scaffold can be manipulated both genetically and chemically to simultaneously display targeting groups and carry a functional payload. Here, we displayed the human epidermal growth factor (EGF) on the exterior surface of bacteriophage Qβ as a C-terminal genetic fusion to the Qβ capsid protein. The co-assembly of wild-type Qβ and EGF-modified subunits resulted in structurally homogeneous nanoparticles displaying between 5 and 12 copies of EGF on their exterior surface. The particles were found to be amenable to bioconjugation by standard methods as well as the high-fidelity copper-catalyzed azide-alkyne cycloaddition reaction (CuAAC). Such chemical derivatization did not impair the ability of the particles to specifically interact with the EGF receptor. Additionally, the particle-displayed EGF remained biologically active promoting autophosphorylation of the EGF receptor and apoptosis of A431 cells. These results suggest that hybrid Qβ-EGF nanoparticles could be useful vehicles for targeted delivery of imaging and/or therapeutic agents.