Effects of human serum on the stability and cytotoxicity of silver nanoparticles

Abstract

Silver nanoparticles are ubiquitous in today's commercial marketplace. Despite decades of research, there is still disagreement about the risk that silver nanoparticles pose to human and environmental health. There is often a lack of correlation between measured physical properties and the measured biological endpoints, making it difficult to establish trends, and discrepancies between different cell models have not been clearly accounted for. Here we have used human AB serum in cell culture media for the investigation in place of fetal bovine serum (FBS) which is typically used. In HepG2 cells, particle uptake was clearly correlated with smaller sizes of particles and with increased cytotoxicity. In neuron-like SH-SY5Y cells, similar trends were not observed. Compared with previously published data on the same particles in these cell lines with cell culture media supplemented with FBS, there are clear and significant differences in the stability of the particles, their cellular uptake and their cytotoxicity in these two commonly used cell models for in vitro cytotoxicity testing. This highlights the need for improved in vitro testing for nanomaterials and the importance of using human serum to better predict human in vivo outcomes.

Physical Characterization and Cellular Toxicity Studies of Commercial NiO Nanoparticles

“…These interactions can cause particles to agglomerate, cause agglomerated particles to redisperse, or facilitate the dissolution of the particles by removing surface atoms. The rates of these processes are dependent on the composition of the serum (for example, which species it comes from) and its concentration [ 32 , 33 ]. Higher serum concentrations have a greater capacity to chelate free metal ions and may reduce cytotoxicity from dissolved ions.…”

“…The Ni-08 dispersion, the best dispersed sample in water, was able to maintain a submicron size for 3 days, although the high PDI values prevented a proper quantitative assessment. While we have previously used DLS measurements in cell culture medium to measure changes in silver nanoparticle dispersions, these heavily agglomerated NiO particles were not well-suited for this approach [ 32 , 33 ].…”

Coated Silver Nanoparticles Exhibit Unique Stability and Cytotoxicity in Media with Human Serum

“…We have previously noted that particles treated with human serum albumin are more stable than those coated with bovine serum albumin, the most abundant proteins in sera [26]. We have also shown that the size dependent stability of silver particles changes in media supplemented with human serum [27]. Here we have tested how commercial particles with different coatings behave in media with human proteins and biomolecules as opposed to those from fetal bovine serum, how the particles evolve over time and how that affects their uptake and cytotoxicty.…”

The Impact of Serum Protein Adsorption on PEGylated NT3–BDNF Nanoparticles—Distribution, Protein Release, and Cytotoxicity in a Human Retinal Pigmented Epithelial Cell Model

“…Neurotrophic factors have been identified as potentially therapeutic agents owing to their protective properties for photoreceptors in models of retinal and neuronal degeneration [ 1 , 2 , 3 ]. Neurotrophins (NTs), including brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3), bind to their tropomyosin-related receptor kinase (TrkB and TrkC) and promote neuronal differentiation, survival, and plasticity [ 4 , 5 ].…”