Natalie V. Hudson-Smith

Research highlights: unveiling the mechanisms underlying nanoparticle-induced ROS generation and oxidative stress

The field of nanotoxicology has a long-tested hypothesis, supported by a significant body of evidence, that nanoparticle-induced reactive oxygen species (ROS) lead to oxidative stress in biological systems. Within this paradigm, it is critical to fundamentally understand the underpinning mechanisms of nanoparticle ROS production and the corresponding oxidative stress they induce. This Highlight is focused on four recent articles on this topic. The first highlighted work investigated ROS generation from various silica nanoparticle surfaces and demonstrated that porosity and surface functionalization are key factors influencing ROS generation and nanoparticle toxicity. The second article demonstrated plasmon-mediated ROS production via hot electron production on gold nanocage surfaces under near-infrared irradiation. The third highlighted work correlated electronic properties of metal oxide nanoparticles to ROS generation, and built a quantitative linear relationship between ROS generation and antibacterial activity. Finally, the fourth study provided insights regarding protein signatures and pathways sensitive to oxidative stress in macrophage cells using a redox proteomic approach. Together, these four reports reveal mechanisms underlying nanoparticle-induced ROS generation and the resulting cellular oxidative stress.

Growth-Based Bacterial Viability Assay for Interference-Free and High-Throughput Toxicity Screening of Nanomaterials

Current high-throughput approaches evaluating toxicity of chemical agents toward bacteria typically rely on optical assays, such as luminescence and absorbance, to probe the viability of the bacteria. However, when applied to toxicity induced by nanomaterials, scattering and absorbance from the nanomaterials act as interferences that complicate quantitative analysis. Herein, we describe a bacterial viability assay that is free of optical interference from nanomaterials and can be performed in a high-throughput format on 96-well plates. In this assay, bacteria were exposed to various materials and then diluted by a large factor into fresh growth medium. The large dilution ensured minimal optical interference from the nanomaterial when reading optical density, and the residue left from the exposure mixture after dilution was confirmed not to impact the bacterial growth profile. The fractions of viable cells after exposure were allowed to grow in fresh medium to generate measurable growth curves. Bacterial viability was then quantitatively correlated to the delay of bacterial growth compared to a reference regarded as 100% viable cells; data analysis was inspired by that in quantitative polymerase chain reactions, where the delay in the amplification curve is correlated to the starting amount of the template nucleic acid. Fast and robust data analysis was achieved by developing computer algorithms carried out using R. This method was tested on four bacterial strains, including both Gram-negative and Gram-positive bacteria, showing great potential for application to all culturable bacterial strains. With the increasing diversity of engineered nanomaterials being considered for large-scale use, this high-throughput screening method will facilitate rapid screening of nanomaterial toxicity and thus inform the risk assessment of nanoparticles in a timely fashion.

Influence of nickel manganese cobalt oxide nanoparticle composition on toxicity toward Shewanella oneidensis MR-1: redesigning for reduced biological impact

Lithium nickel manganese cobalt oxide (LixNiyMnzCo1−y−zO2, 0 < x, y, z < 1, also known as NMC) is a class of cathode materials used in lithium ion batteries. Despite the increasing use of NMC in nanoparticle form for next-generation energy storage applications, the potential environmental impact of released nanoscale NMC is not well characterized. Previously, we showed that the released nickel and cobalt ions from nanoscale Li1/3Ni1/3Mn1/3Co1/3O2 were largely responsible for impacting the growth and survival of the Gram-negative bacterium Shewanella oneidensis MR-1 (M. N. Hang et al., Chem. Mater., 2016, 28, 1092). Here, we show the first steps toward material redesign of NMC to mitigate its biological impact and to determine how the chemical composition of NMC can significantly alter the biological impact on S. oneidensis. We first synthesized NMC with various stoichiometries, with an aim to reduce the Ni and Co content: Li0.68Ni0.31Mn0.39Co0.30O2, Li0.61Ni0.23Mn0.55Co0.22O2, and Li0.52Ni0.14Mn0.72Co0.14O2. Then, S. oneidensis were exposed to 5 mg L−1 of these NMC formulations, and the impact on bacterial oxygen consumption was analyzed. Measurements of the NMC composition, by X-ray photoelectron spectroscopy, and composition of the nanoparticle suspension aqueous phase, by inductively coupled plasma-optical emission spectroscopy, showed the release of Li, Ni, Mn, and Co ions. Bacterial inhibition due to redesigned NMC exposure can be ascribed largely to the impact of ionic metal species released from the NMC, most notably Ni and Co. Tuning the NMC stoichiometry to have increased Mn at the expense of Ni and Co showed lowered, but not completely mitigated, biological impact. This study reveals that the chemical composition of NMC nanomaterials is an important parameter to consider in sustainable material design and usage.

Research highlights: speciation and transformations of silver released from Ag NPs in three species

Antimicrobial silver nanoparticles used in consumer products may be released during fabrication, during product use, or after disposal and may reach terrestrial and aquatic ecosystems, prompting concern about their potential to adversely impact the environment (Benn and Westerhoff, Environ. Sci. Technol., 2008, 42, 4133, DOI: 10.1021/es7032718). Although the toxicity of pristine silver nanoparticles is well studied and understood, silver nanoparticles can undergo transformation during release and in engineered and natural environments. The speciation of silver after release must therefore be explored to deepen understanding of the potential impact of these nanoparticles on the environment. Herein, we highlight three articles which use highly sensitive analytical techniques to define, and in some cases map, silver speciation in situ after exposure to organisms of varying size and complexity. First, we highlight research by Leonardo et al. which explores the transformations of silver acted upon by a microalgae species that is a candidate for heavy metal remediation in water. Next, we highlight research by Stegemeier et al. quantifying and mapping the speciation of silver in alfalfa after exposure to several silver sources, including two silver-based nanoparticles. Finally, we discuss work by Wang et al. on silver speciation in human monocyte cells as observed by synchrotron radiation techniques which leads to mechanistic insights on cytotoxicity.

Molecular Affinity Agents for Intrinsic Surface-Enhanced Raman Scattering (SERS) Sensors

Research at the interface of synthetic materials, biochemistry, and analytical techniques has enabled sensing platforms for applications across many research communities. Herein we review the materials used as affinity agents to create surface-enhanced Raman spectroscopy (SERS) sensors. Our scope includes those affinity agents (antibody, aptamer, small molecule, and polymer) that facilitate the intrinsic detection of targets relevant to biology, medicine, national security, environmental protection, and food safety. We begin with an overview of the analytical technique (SERS) and considerations for its application as a sensor. We subsequently describe four classes of affinity agents, giving a brief overview on affinity, production, attachment chemistry, and first uses with SERS. Additionally, we review the SERS features of the affinity agents, and the analytes detected by intrinsic SERS with that affinity agent class. We conclude with remarks on affinity agent selection for intrinsic SERS sensing platforms.

Research highlights: comparing the biological response of nanoparticle solid solutions

Scientific advances in the field of nanotechnology have led to the wide-scale use of engineered nanomaterials, resulting in an increased demand to understand the biological impact of these materials when released to the environment. This demand has led to an evolving field of science focused specifically on interactions at the nano–bio interface, where researchers investigate the biological responses of a wide range of organisms to engineered nanomaterials. The majority of investigations into the nano–bio interface are focused on the biological response of single-phase nanomaterials, yet engineered nanomaterials are often more complex than a single-phase nanomaterial. Many engineered nanomaterials can be described as solid solutions (or alloys) where multiple types of cations (and/or anions) are present in different ratios, and properties such as spin state, valence charge, and lattice constant can be tuned by changing the atomic composition. Research at the nano–bio interface must go beyond investigating the biological response of single-phase nanomaterials and include a systematic approach to predict how the biological interactions of nanomaterial solid solutions can be controlled via systematic changes in chemical composition. In this highlight, we focus on four publications that use a range of experimental methods to delineate the interactions of solid solutions composed of either Au metal or ZnO solid oxide on a variety of organisms. The first highlighted work tunes the composition of Au–Pt nanoparticles for antibacterial activity. The second article investigates the reprotoxicity of Au–Ag nanoparticles. The third highlighted work shows that Fe–ZnO nanoparticles demonstrate a reduced toxicity when compared to ZnO. Finally, the fourth study presents an in silico design strategy for cancer specific Fe–ZnO nanoparticles. Together, these four studies reveal the wide range of chemical compositions that are accessible in nanomaterial solid solutions and demonstrate that careful modifications in compositional phase space can result in selective nano–bio interactions.