Inducing cancer cell death by targeting its nucleus: solid gold nanospheres versus hollow gold nanocages

Bioconjug Chem. 2013 Jun 19;24(6):897-906. doi: 10.1021/bc300592d. Epub 2013 Jun 10.

Abstract

Recently, we have shown that targeting the cancer cell nucleus with solid gold nanospheres, using a cancer cell penetrating/pro-apoptotic peptide (RGD) and a nuclear localization sequence peptide (NLS), inhibits cell division, thus leading to apoptosis. In the present work, flow cytometric analysis revealed an increase in cell death, via apoptosis and necrosis, in HSC cells upon treatment with peptide-conjugated hollow gold nanocages, compared to those treated with the peptide-conjugated solid gold nanospheres. This is consistent with a G0/G1 phase accumulation, S phase depletion, and G2/M phase depletion, as well as reduced ATP levels. Here, we investigate the possible causes for the observed enhanced cell death with the use of confocal microscopy. The fluorescence images of HSC cells treated with gold nanocages indicate the presence of reactive oxygen species, known to cause apoptosis. The formation of reactive oxygen species observed is consistent with a mechanism involving the oxidation of metallic silver on the inner cavity of the nanocage (inherent to the synthesis of the gold nanocages) to silver oxide. This oxidation is confirmed by an observed redshift in the surface plasmon resonance of the gold nanocages in cell culture medium. The silver oxide, a semiconductor known to photochemically generate hydroxyl radicals, a form of reactive oxygen species, is proposed as a mechanism for the enhanced cell death caused by gold nanocages. Thus, the enhanced cell death, via apoptosis and necrosis, observed with peptide-conjugated hollow gold nanocage-treated cells is considered to be a result of the metallic composition (silver remaining on the inner cavity) of the nanocage.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / pathology
  • Cell Cycle / drug effects
  • Cell Death / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Gold / chemistry*
  • Humans
  • Metal Nanoparticles / chemistry*
  • Mouth Neoplasms / drug therapy*
  • Mouth Neoplasms / pathology
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology*
  • Particle Size
  • Peptides / chemistry*
  • Porosity
  • Structure-Activity Relationship
  • Surface Properties

Substances

  • Antineoplastic Agents
  • Organometallic Compounds
  • Peptides
  • Gold