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Timescale of Silver Nanoparticle Transformation in Neural Cell Cultures Impacts Measured Cell Response



Stephanie L. Hume, Ann Chiaramonti Debay, Katherine P. Rice, Rani K. Schwindt, Robert I. MacCuspie, Kavita Jeerage


Serum protein concentration and ionic strength are important factors in nanoparticle transformation within cell culture environments. However, silver nanoparticles are not routinely tracked at their working concentration in the specific medium used for in vitro toxicology studies. Here we evaluated the transformation of electrostatically stabilized citrate nanoparticles (C-AgNPs) and sterically stabilized polyvinylpyrrolidone nanoparticles (PVP-AgNPs) in a low-serum ( 0.2 mg/mL bovine serum albumin) medium, while measuring the response of neural progenitor cells undergoing differentiation. After 24 h, silver nanoparticles at concentrations up to 10 µg/mL did not affect adenosine triphosphate levels, whereas silver ions decreased adenosine triphosphate levels at concentrations of 1.1 µg/mL or higher. After 240 h, both silver nanoparticles, and silver ion, unambiguously decreased adenosine triphosphate levels at concentrations of 1 µg/mL and 1.1 µg/mL, respectively, suggesting particle dissolution. Particle transformation was investigated in 1:10 diluted, 1:2 diluted, or undiluted differentiation medium, all having an identical protein concentration, to separate the effect of serum protein stabilization from ionic strength destabilization. Transmission electron microscopy images indicated that particles in 1:10 medium were not surrounded by proteins, whereas particles became clustered within a non-crystalline protein matrix after 24 h in 1:2 medium and at 0 h in undiluted medium. Despite evidence for a protein corona, particles were rapidly destabilized by high ionic strength media. Polyvinylpyrrolidone increased the stability of singly-dispersed particles compared to citrate ligands; however, differences were negligible after 4 h in 1:2 medium or after 1 h in undiluted medium. Thus low-serum culture environments do not provide sufficient colloidal stability for long-term toxicology studies with citrate or polyvinylpyrrolidone stabilized silver nanoparticles.
Journal of Nanoparticle Research


silver nanoparticles, neurite outgrowth, progenitor cells, lithium chloride


Hume, S. , Chiaramonti Debay, A. , Rice, K. , Schwindt, R. , MacCuspie, R. and Jeerage, K. (2015), Timescale of Silver Nanoparticle Transformation in Neural Cell Cultures Impacts Measured Cell Response, Journal of Nanoparticle Research, [online],, (Accessed July 20, 2024)


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Created July 6, 2015, Updated October 12, 2021