title: Multifunctional gold nanoparticle-peptide complexes for nuclear targeting.
abstract: The ability of peptide-modified gold nanoparticles to target the nucleus of HepG2 cells was explored. Five peptide/nanoparticle complexes were investigated, particles modified with (1) the nuclear localization signal (NLS) from the SV 40 virus; (2) the adenovirus NLS; (3) the adenovirus receptor-mediated endocytosis (RME) peptide; (4) one long peptide containing the adenovirus RME and NLS; and (5) the adenovirus RME and NLS peptides attached to the nanoparticle as separate pieces. Gold nanoparticles were used because they are easy to identify using video-enhanced color differential interference contrast microscopy, and they are excellent scaffolds from which to build multifunctional nuclear targeting vectors. For example, particles modified solely with NLS peptides were not able to target the nucleus of HepG2 cells from outside the plasma membrane, because they either could not enter the cell or were trapped in endosomes. The combination of NLS/RME particles (4) and (5) did reach the nucleus; however, nuclear targeting was more efficient when the two signals were attached to nanoparticles as separate short pieces versus one long peptide. These studies highlight the challenges associated with nuclear targeting and the potential advantages of designing multifunctional nanostructured materials as tools for intracellular diagnostics and therapeutic delivery.
authors.affiliation: Department of Chemistry, North Carolina State Univ, Raleigh, North Carolina 27695, USA.
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Tkachenko
authors.forename: Huan
authors.initials: H
authors.lastname: Xie
authors.forename: Donna
authors.initials: D
authors.lastname: Coleman
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Glomm
authors.forename: Joseph
authors.initials: J
authors.lastname: Ryan
authors.forename: Miles F
authors.initials: MF
authors.lastname: Anderson
authors.forename: Stefan
authors.initials: S
authors.lastname: Franzen
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Feldheim
mesh_terms: D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000378:metabolism*; D006046:Gold / Q000737:chemistry* / Q000493:pharmacokinetics*; D006801:Humans; D008969:Molecular Sequence Data; D036103:Nanotechnology / Q000379:methods; D009842:Oligopeptides / Q000737:chemistry* / Q000493:pharmacokinetics*; D010316:Particle Size; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000493:pharmacokinetics; D014407:Tumor Cells, Cultured
chemical_list: D009842:Oligopeptides; D012710:Serum Albumin, Bovine; D006046:Gold