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Cell Targeting With Hybrid Qβ Virus‐Like Particles Displaying Epidermal Growth Factor

J. Pokorski, Marisa L. Hovlid, M. Finn
Published 2011 · Chemistry, Medicine

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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.
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