Mechanism of cellular uptake of genotoxic silica nanoparticles.

ABSTRACT: Mechanisms for cellular uptake of nanoparticles have important implications for nanoparticulate drug delivery and toxicity. We have explored the mechanism of uptake of amorphous silica nanoparticles of 14?nm diameter, which agglomerate in culture medium to hydrodynamic diameters around 500?nm. In HT29, HaCat and A549 cells, cytotoxicity was observed at nanoparticle concentrations ? 1??g/ml, but DNA damage was evident at 0.1??g/ml and above. Transmission electron microscopy (TEM) combined with energy-dispersive X-ray spectroscopy confirmed entry of the silica particles into A549 cells exposed to 10??g/ml of nanoparticles. The particles were observed in the cytoplasm but not within membrane bound vesicles or in the nucleus. TEM of cells exposed to nanoparticles at 4°C for 30 minutes showed particles enter cells when activity is low, suggesting a passive mode of entry. Plasma lipid membrane models identified physical interactions between the membrane and the silica NPs. Quartz crystal microbalance experiments on tethered bilayer lipid membrane systems show that the nanoparticles strongly bind to lipid membranes, forming an adherent monolayer on the membrane. Leakage assays on large unilamellar vesicles (400?nm diameter) indicate that binding of the silica NPs transiently disrupts the vesicles which rapidly self-seal. We suggest that an adhesive interaction between silica nanoparticles and lipid membranes could cause passive cellular uptake of the particles.

SUBMITTER: Mu Q 

PROVIDER: S-EPMC3479067 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature