Caspase 3 Independent Cell Death Induced by Amorphous Silica Nanoparticles

The molecular mechanisms of cell death induced by amorphous silica nanoparticles of 50 and 200 nm in diameter were investigated. Confocal microscopy revealed differential intracellular localization of plain, amine- or carboxyl-terminated silica nanoparticles in RAW 264.7 macrophages. Toxicological effects of silica nanoparticles depended both on particle size and the presence of surface functional groups. All tested silica nanoparticles caused mitochondrial membrane depolarization to various degrees. Incubation of macrophages with silica nanoparticles resulted in the activation of p53 and changed the ratio of pro/anti-apoptotic Bcl-2 family proteins but did not induce caspase-3 activation or Poly(ADP-ribose) polymerase-1 cleavage. It is concluded that plasma membrane damage and mitochondrial dysfunction are prime mechanisms of cell death induced by the tested amorphous silica nanoparticles.