title: Guiding plant virus particles to integrin-displaying cells.
abstract: Viral nanoparticles (VNPs) are structurally regular, highly stable, tunable nanomaterials that can be conveniently produced in high yields. Unmodified VNPs from plants and bacteria generally do not show tissue specificity or high selectivity in binding to or entry into mammalian cells. They are, however, malleable by both genetic and chemical means, making them useful scaffolds for the display of large numbers of cell- and tissue-targeting ligands, imaging moieties, and/or therapeutic agents in a well-defined manner. Capitalizing on this attribute, we modified the genetic sequence of the Cowpea mosaic virus (CPMV) coat protein to display an RGD oligopeptide sequence derived from human adenovirus type 2 (HAdV-2). Concurrently, wild-type CPMV was modified via NHS acylation and Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) chemistry to attach an integrin-binding cyclic RGD peptide. Both types of particles showed strong and selective affinity for several different cancer cell lines that express RGD-binding integrin receptors.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA.
authors.forename: Marisa L
authors.initials: ML
authors.lastname: Hovlid
authors.forename: Nicole F
authors.initials: NF
authors.lastname: Steinmetz
authors.forename: Burkhardt
authors.initials: B
authors.lastname: Laufer
authors.forename: Jolene L
authors.initials: JL
authors.lastname: Lau
authors.forename: Jane
authors.initials: J
authors.lastname: Kuzelka
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Timo
authors.initials: T
authors.lastname: Hyypiä
authors.forename: Glen R
authors.initials: GR
authors.lastname: Nemerow
authors.forename: Horst
authors.initials: H
authors.lastname: Kessler
authors.forename: Marianne
authors.initials: M
authors.lastname: Manchester
authors.forename: M G
authors.initials: MG
authors.lastname: Finn
mesh_terms: D000256:Adenoviridae / Q000378:metabolism; D000480:Alkynes / Q000737:chemistry; D001386:Azides / Q000737:chemistry; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002384:Catalysis; D045744:Cell Line, Tumor; D017798:Comovirus / Q000378:metabolism*; D003300:Copper / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D000480:Alkynes; D001386:Azides; D036022:Capsid Proteins; D016023:Integrins; D009842:Oligopeptides; D003300:Copper; C047981:arginyl-glycyl-aspartic acid