When function is biological: Discerning how silver nanoparticle structure dictates antimicrobial activity.

Silver nanomaterials have potent antibacterial properties that are the foundation for their wide commercial use as well as for concerns about their unintended environmental impact. The nanoparticles themselves are relatively biologically inert but they can undergo oxidative dissolution yielding toxic silver ions. A quantitative relationship between silver material structure and dissolution, and thus antimicrobial activity, has yet to be established. Here, this dissolution process and associated biological activity is characterized using uniform nanoparticles with variable dimension, shape, and surface chemistry. From this, a phenomenological model emerges that quantitatively relates material structure to both silver dissolution and microbial toxicity. Shape has the most profound influence on antibacterial activity, and surprisingly, surface coatings the least. These results illustrate how material structure may be optimized for antimicrobial properties and suggest strategies for minimizing silver nanoparticle effects on microbes.

Size-dependent impacts of silver nanoparticles on the lifespan, fertility, growth, and locomotion of Caenorhabditis elegans.

The increased bioavailability of nanoparticles engineered for good dispersion in water may have biological and environmental impacts. To examine this issue, the authors assessed the biological effects in nematodes as they relate to exposure to silver nanoparticles (AgNPs) of different sizes at low (1 mg/L Ag), medium (10 mg/L Ag), and high concentrations (100 mg/L Ag). Over multiple generations, the authors found that the smallest particle, at 2 nm, had a notable impact on nematode fertility. In contrast, the largest particle, at 10 nm, significantly reduced the lifespan of parent nematodes (P0 ) by 28.8% and over the span of 3 generations (F1 -F3). In addition, a computer vision system automatically measured the adverse effects in body length and motility, which were not size-dependent.

Antioxidant properties of cerium oxide nanocrystals as a function of nanocrystal diameter and surface coating.

This work examines the effect of nanocrystal diameter and surface coating on the reactivity of cerium oxide nanocrystals with H2O2 both in chemical solutions and in cells. Monodisperse nanocrystals were formed in organic solvents from the decomposition of cerium precursors, and subsequently phase transferred into water using amphiphiles as nanoparticle coatings. Quantitative analysis of the antioxidant capacity of CeO2-x using gas chromatography and a luminol test revealed that 2 mol of H2O2 reacted with every mole of cerium(III), suggesting that the reaction proceeds via a Fenton-type mechanism. Smaller diameter nanocrystals containing more cerium(III) were found to be more reactive toward H2O2. Additionally, the presence of a surface coating did not preclude the reaction between the nanocrystal surface cerium(III) and hydrogen peroxide. Taken together, the most reactive nanoparticles were the smallest (e.g., 3.8 nm diameter) with the thinnest surface coating (e.g., oleic acid). Moreover, a benchmark test of their antioxidant capacity revealed these materials were 9 times more reactive than commercial antioxidants such as Trolox. A unique feature of these antioxidant nanocrystals is that they can be applied multiple times: over weeks, cerium(IV) rich particles slowly return to their starting cerium(III) content. In nearly all cases, the particles remain colloidally stable (e.g., nonaggregated) and could be applied multiple times as antioxidants. These chemical properties were also observed in cell culture, where the materials were able to reduce oxidative stress in human dermal fibroblasts exposed to H2O2 with efficiency comparable to their solution phase reactivity. These data suggest that organic coatings on cerium oxide nanocrystals do not limit the antioxidant behavior of the nanocrystals, and that their redox cycling behavior can be preserved even when stabilized.

Silver nanoparticle toxicity to Daphnia magna is a function of dissolved silver concentration.

The most persistent question regarding the toxicity of silver nanoparticles (AgNPs) is whether this toxicity is due to the nanoparticles themselves or the silver ions (Ag(+)) they release. The present study investigates the role of surface coating and the presence of dissolved organic carbon on the toxicity of AgNPs to Daphnia magna and tests the hypothesis that the acute toxicity of AgNPs is a function of dissolved Ag produced by nanoparticle dissolution. Toxicity of silver nitrate (AgNO3) and AgNPs with surface coatings-gum arabic (AgGA), polyethylene glycol (AgPEG), and polyvinylpyrrolidone (AgPVP)-at 48 h was assessed in US Environmental Protection Agency moderately hard reconstituted water alone and augmented with Suwannee River dissolved organic carbon (DOC). As expected, AgNO3 was the most toxic to D. magna and AgPVPs were the least toxic. In general, Suwannee River DOC presence reduced the toxicity of AgNO3, AgGAs, and AgPEG, while the toxicity of AgPVPs was unaffected. The measured dissolved Ag concentrations for all AgNPs and AgNO3 at the 48-h median lethal concentration in moderately hard reconstituted water were similar. The presence of Suwannee River DOC decreased the ratio of measured dissolved Ag to measured total Ag concentration. These results support the hypothesis that toxicity of AgNPs to D. magna is a function of dissolved Ag concentration from these particles.

Toxicity of quantum dots and cadmium salt to Caenorhabditis elegans after multigenerational exposure.

To fully understand the biological and environmental impacts of nanomaterials requires studies that address both sublethal end points and multigenerational effects. Here, we use a nematode to examine these issues as they relate to exposure to two different types of quantum dots, core (CdSe) and core-shell (CdSe/ZnS), and to compare the effect to those observed after cadmium salt exposures. The strong fluorescence of the core-shell QDs allowed for the direct visualization of the materials in the digestive track within a few hours of exposure. Multiple end points, including both developmental and locomotive, were examined at QD exposures of low (10 mg/L Cd), medium (50 mg/L Cd), and high concentrations (100 mg/L Cd). While the core-shell QDs showed no effect on fitness (lifespan, fertility, growth, and three parameters of motility behavior), the core QDs caused acute effects similar to those found for cadmium salts, suggesting that biological effects may be attributed to cadmium leaching from the more soluble QDs. Over multiple generations, we commonly found that for lower life-cycle exposures to core QDs the parents response was generally a poor predictor of the effects on progeny. At the highest concentrations, however, biological effects found for the first generation were commonly similar in magnitude to those found in future generations.

Negligible particle-specific antibacterial activity of silver nanoparticles.

For nearly a decade, researchers have debated the mechanisms by which AgNPs exert toxicity to bacteria and other organisms. The most elusive question has been whether the AgNPs exert direct "particle-specific" effects beyond the known antimicrobial activity of released silver ions (Ag(+)). Here, we infer that Ag(+) is the definitive molecular toxicant. We rule out direct particle-specific biological effects by showing the lack of toxicity of AgNPs when synthesized and tested under strictly anaerobic conditions that preclude Ag(0) oxidation and Ag(+) release. Furthermore, we demonstrate that the toxicity of various AgNPs (PEG- or PVP- coated, of three different sizes each) accurately follows the dose-response pattern of E. coli exposed to Ag(+) (added as AgNO(3)). Surprisingly, E. coli survival was stimulated by relatively low (sublethal) concentration of all tested AgNPs and AgNO(3) (at 3-8 µg/L Ag(+), or 12-31% of the minimum lethal concentration (MLC)), suggesting a hormetic response that would be counterproductive to antimicrobial applications. Overall, this work suggests that AgNP morphological properties known to affect antimicrobial activity are indirect effectors that primarily influence Ag(+) release. Accordingly, antibacterial activity could be controlled (and environmental impacts could be mitigated) by modulating Ag(+) release, possibly through manipulation of oxygen availability, particle size, shape, and/or type of coating.