title: 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.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Jonathan K
authors.initials: JK
authors.lastname: Pokorski
authors.forename: Marisa L
authors.initials: ML
authors.lastname: Hovlid
authors.forename: M G
authors.initials: MG
authors.lastname: Finn
mesh_terms: D000480:Alkynes / Q000737:chemistry; D017908:Allolevivirus / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D001386:Azides / Q000737:chemistry; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism; D002384:Catalysis; D045744:Cell Line, Tumor; D003300:Copper / Q000737:chemistry; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D006834:Hydrazines / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry; D010766:Phosphorylation; D011485:Protein Binding
chemical_list: C417561:Alexa 488 hydrazide; D000480:Alkynes; D001386:Azides; D036022:Capsid Proteins; D006834:Hydrazines; D004815:Epidermal Growth Factor; D003300:Copper; D066246:ErbB Receptors