Cytotoxicity Induced by Engineered Silver Nanocrystallites Is Dependent on Surface Coatings and Cell Types

Abstract

Due to their unique antimicrobial properties silver nanocrystallites have garnered substantial attention and are used extensively for biomedical applications as an additive to wound dressings, surgical instruments and bone substitute materials. They are also released into unintended locations such as the environment or biosphere. Therefore it is imperative to understand the potential interactions, fate and transport of nanoparticles with environmental biotic systems. Numerous factors including the composition, size, shape, surface charge, and capping molecule of nanoparticles are known to influence cell cytotoxicity. Our results demonstrate that the physical/chemical properties of the silver nanoparticles including surface charge, differential binding and aggregation potential, which are influenced by the surface coatings, are a major determining factor in eliciting cytotoxicity and in dictating potential cellular interactions. In the present investigation, silver nanocrystallites with nearly uniform size and shape distribution but with different surface coatings, imparting overall high negativity to high positivity, were synthesized. These nanoparticles included poly(diallyldimethylammonium) chloride-Ag, biogenic-Ag, colloidal-Ag (uncoated), and oleate-Ag with zeta potentials +45 ± 5, -12 ± 2, -42 ± 5, and -45 ± 5 mV, respectively; the particles were purified and thoroughly characterized so as to avoid false cytotoxicity interpretations. A systematic investigation on the cytotoxic effects, cellular response, and membrane damage caused by these four different silver nanoparticles was carried out using multiple toxicity measurements on mouse macrophage (RAW-264.7) and lung epithelial (C-10) cell lines. Our results clearly indicate that the cytotoxicity was dependent on various factors such as surface charge and coating materials used in the synthesis, particle aggregation, and the cell-type for the different silver nanoparticles that were investigated. Poly(diallyldimethylammonium)-coated Ag nanoparticles were found to be the most toxic, followed by biogenic-Ag and oleate-Ag nanoparticles, whereas uncoated or colloidal silver nanoparticles were found to be the least toxic to both macrophage and lung epithelial cells. Also, based on our cytotoxicity interpretations, lung epithelial cells were found to be more resistant to the silver nanoparticles than the macrophage cells, regardless of the surface coating.

Comparative assessment of the apoptotic potential of silver nanoparticles synthesized by Bacillus tequilensis and Calocybe indica in MDA-MB-231 human breast cancer cells: targeting p53 for anticancer therapy

“…The significant toxicity of F-AgNPs may be due to the overall surface charge and/or surface coating of AgNPs. 61 Our studies are consistent with previous studies showing that AgNPs exposure can induce changes in cell shape, reduce cell viability, and increase lactate dehydrogenase (LDH) release, and finally, result in cell apoptosis and necrosis. 8,20,[64][65][66][67] Edetsberger et al demonstrated that AgNPs with a size of #20 nm could enter cells without significant endocytosis and were distributed within the cytoplasm.…”

Silver nanoparticle toxicity is related to coating materials and disruption of sodium concentration regulation

“…Moreover, toxicity of AgNPs with different coating materials followed the same order observed in our study: GA > PVP > Cit AgNP (Yang et al 2012). Coating materials and surface charge-dependent AgNP cytotoxicity was also observed by Suresh et al (2012). Similar findings have been reported in toxicity of gold nanoparticles as well (Truong et al 2013), suggesting that this coating effect J U S T A C C E P T E D might apply to other metallic NPs.…”

“…However, these conclusions were partially confounded by the different particle sizes of the AgNPs. While other studies confirm that coatings of AgNP can affect toxicity in cells and invertebrates (Yang et al 2012;Suresh et al 2012;Zhao and Wang 2012) whether this effect extends to vertebrates is unknown. To better understand mechanisms of toxicity of AgNPs in aquatic environment and the effect of coatings, this study systematically compared toxicity of 10 different AgNPs with different coatings and sizes in an aquarium model J U S T A C C E P T E D fish, relating their toxicities with AgNP characteristics and properties in test media, and the underlying mechanism of toxicity.…”

Controlling release kinetics of gentamicin from silica nano-carriers

“…The pH resulting in half of the groups protonation (and half of the groups deprotonation) corresponds to the value of pKa of the dissociation reaction (HendersonHasslbach equation). Cells are generally negatively charged hence strong electrostatic interactions would be originated towards positively charged particles, however surfaces appendices present on cell can overcome the possible repulsive barrier observed when facing negatively charged surfaces; evidence has shown that positively nanoparticles have higher toxicity than negatively charged ones [45]. Human body pH is generally close to neutral, however there are some fluids that exhibit extreme acidity (stomach is about pH = 3.5 [46]) or alkalinity (pancreatic fluid is about pH = 8.8 [47]) therefore the pH range employed for our studies covers such spectrum.…”