Nanotoxicology Research Research Articles

Bacterial Susceptibility to Ceria Nanoparticles: The Critical Role of Surrounding Molecules.

Investigating the ternary relationship among nanoparticles (NPs), their immediate molecular environment, and test organisms rather than the direct interaction between pristine NPs and test organisms has been thrust into the mainstream of nanotoxicological research. Diverging from previous work that predominantly centered on surrounding molecules affecting the toxicity of NPs by modulating their nanoproperties, this study has unveiled a novel dimension: surrounding molecules altering bacterial susceptibility to NPs, consequently impacting the outcomes of nanobio interaction. The study found that adding nitrate as the surrounding molecules could alter bacterial respiratory pathways, resulting in an enhanced reduction of ceria NPs (nanoceria) on the bacterial surfaces. This, in turn, increased the ion-specific toxicity originating from the release of Ce3+ ions at the nanobio interface. Further transcriptome analysis revealed more mechanistic details underlying the nitrate-induced changes in the bacterial energy metabolism and subsequent toxicity patterns. These findings offer a new perspective for the deconstruction of nanobio interactions and contribute to a more comprehensive understanding of NPs' environmental fate and ecotoxicity.

Molecular mechanism of nanomaterials induced liver injury: A review.

The unique physicochemical properties inherent to nanoscale materials have unveiled numerous potential applications, spanning beyond the pharmaceutical and medical sectors into various consumer industries like food and cosmetics. Consequently, humans encounter nanomaterials through diverse exposure routes, giving rise to potential health considerations. Noteworthy among these materials are silica and specific metallic nanoparticles, extensively utilized in consumer products, which have garnered substantial attention due to their propensity to accumulate and induce adverse effects in the liver. This review paper aims to provide an exhaustive examination of the molecular mechanisms underpinning nanomaterial-induced hepatotoxicity, drawing insights from both in vitro and in vivo studies. Primarily, the most frequently observed manifestations of toxicity following the exposure of cells or animal models to various nanomaterials involve the initiation of oxidative stress and inflammation. Additionally, we delve into the existing in vitro models employed for evaluating the hepatotoxic effects of nanomaterials, emphasizing the persistent endeavors to advance and bolster the reliability of these models for nanotoxicology research.

Nanosafety: a Perspective on Nano-Bio Interactions.

Engineered nanomaterials offer numerous benefits to society ranging from environmental remediation to biomedical applications such as drug or vaccine delivery as well as clean and cost-effective energy production and storage, and the promise of a more sustainable way of life. However, as nanomaterials of increasing sophistication enter the market, close attention to potential adverse effects on human health and the environment is needed. Here a critical perspective on nanotoxicological research is provided; the authors argue that it is time to leverage the knowledge regarding the biological interactions of nanomaterials to achieve a more comprehensive understanding of the human health and environmental impacts of these materials. Moreover, it is posited that nanomaterials behave like biological entities and that they should be regulated as such.

Research Status of Nanomaterial Medical Device and Discussion on Biological Evaluation

In recent years, China has made great progress in basic nanomedicine, nanotoxicology and nanobiology research. Nanotechnology has been continuously applied in biomaterial and medical device, more and more medical devices applying nanomaterials are developed and manufactured. In order to gain more comprehension and accurate understanding of the research and industrial development in nanobiomaterial medical devices, this study reviewed the common nanomaterial in medical devices and the regulatory situation of nanomaterial medical devices at home and abroad, and discussed the current challenges in biological evaluation of nanomaterial medical devices, with a view to providing ideas for the safety evaluation and research of related products.

The use of nanoparticles in the treatment of infectious diseases and cancer, dental applications and tissue regeneration: a review.

The emergence of nanotechnology as a field of study can be traced back to the 1980s, at which point the means to artificially produce, control, and observe matter on a nanometer level was made viable. Recent advancements in technology have enabled us to extend our reach to the nanoscale, which has presented an unparalleled opportunity to directly target biomolecular interactions. As a result of these developments, there is a drive to arise intelligent nanostructures capable of overcoming the obstacles that have impeded the progress of conventional pharmacological methodologies. After four decades, the gradual amalgamation of bio- and nanotechnologies is initiating a revolution in the realm of disease detection, treatment, and monitoring, as well as unsolved medical predicaments. Although a significant portion of research in the field is still confined to laboratories, the initial application of nanotechnology as treatments, vaccines, pharmaceuticals, and diagnostic equipment has now obtained endorsement for commercialization and clinical practice. The current issue presents an overview of the latest progress in nanomedical strategies towards alleviating antibiotic resistance, diagnosing and treating cancer, addressing neurodegenerative disorders, and an array of applications, encompassing dentistry and tuberculosis treatment. The current investigation also scrutinizes the deployment of sophisticated smart nanostructured materials in fields of application such as regenerative medicine, as well as the management of targeted and sustained release of pharmaceuticals and therapeutic interventions. The aforementioned concept exhibits the potential for revolutionary advancements within the field of immunotherapy, as it introduces the utilization of implanted vaccine technology to consistently regulate and augment immune functions. Concurrently with the endeavor to attain the advantages of nanomedical intervention, it is essential to enhance the unceasing emphasis on nanotoxicological research and the regulation of nanomedications' safety. This initiative is crucial in achieving the advancement in medicine that currently lies within our reach.

Controlling nanoparticle-induced endothelial leakiness with the protein corona.

Understanding nanoparticle-cell interaction is essential for advancing research in nanomedicine and nanotoxicology. Apart from the transcytotic pathway mediated by cellular recognition and energetics, nanoparticles (including nanomedicines) may harness the paracellular route for their transport by inducing endothelial leakiness at cadherin junctions. This phenomenon, termed as NanoEL, is correlated with the physicochemical properties of the nanoparticles in close association with cellular signalling, membrane mechanics, as well as cytoskeletal remodelling. However, nanoparticles in biological systems are transformed by the ubiquitous protein corona and yet the potential effect of the protein corona on NanoEL remains unclear. Using confocal fluorescence microscopy, biolayer interferometry, transwell, toxicity, and molecular inhibition assays, complemented by molecular docking, here we reveal the minimal to significant effects of the anionic human serum albumin and fibrinogen, the charge neutral immunoglobulin G as well as the cationic lysozyme on negating gold nanoparticle-induced endothelial leakiness in vitro and in vivo. This study suggests that nanoparticle-cadherin interaction and hence the extent of NanoEL may be partially controlled by pre-exposing the nanoparticles to plasma proteins of specific charge and topology to facilitate their biomedical applications.

Converting Nanotoxicity Data to Information Using Artificial Intelligence and Simulation.

Decades of nanotoxicology research have generated extensive and diverse data sets. However, data is not equal to information. The question is how to extract critical information buried in vast data streams. Here we show that artificial intelligence (AI) and molecular simulation play key roles in transforming nanotoxicity data into critical information, i.e., constructing the quantitative nanostructure (physicochemical properties)-toxicity relationships, and elucidating the toxicity-related molecular mechanisms. For AI and molecular simulation to realize their full impacts in this mission, several obstacles must be overcome. These include the paucity of high-quality nanomaterials (NMs) and standardized nanotoxicity data, the lack of model-friendly databases, the scarcity of specific and universal nanodescriptors, and the inability to simulate NMs at realistic spatial and temporal scales. This review provides a comprehensive and representative, but not exhaustive, summary of the current capability gaps and tools required to fill these formidable gaps. Specifically, we discuss the applications of AI and molecular simulation, which can address the large-scale data challenge for nanotoxicology research. The need for model-friendly nanotoxicity databases, powerful nanodescriptors, new modeling approaches, molecular mechanism analysis, and design of the next-generation NMs are also critically discussed. Finally, we provide a perspective on future trends and challenges.

Review on aquatic toxicity of metal oxide nanoparticles

Metal oxide nanoparticles are some of the most widely used nanomaterials in the agriculture, consumer products, and energy sectors. Their increased requirements and wide applications can necessarily cause harm to ecosystems and organisms. So, it is vital to understand the main toxicity before they caused harmful effects on the human health. The unique characteristics of nanoengineered materials include carbon fullerenes, carbon nanotubes, metal oxide nanoparticles and quantum dots, among many others have led to the capacity for various toxicities in comparison to the materials in bulk. This review mainly metal oxide nanoparticle can exert adverse effects on humans and aquatic organisms; however, their toxic mechanisms are still unclear. With the well-known consequences of inhaled fine particulate matter, inhalational toxicity is to be expected. Nanotoxicology exhibits a booming research area and aims in finding out their societal or an environmental threat. Ecological factors along with the innatequalities affect nanoparticles (NPs) fate, behavioural and transport, and eventually leading to toxicity. This review examines the research performed in the last two decade to show how metal and metal oxide nanoparticles are influencing the aquatic environment. We addressed here, the physico-chemical characteristics of nanomaterials (NMs), characterization, exposure routes in the aquatic ecosystem. This review summarizes the current understanding and the future possibilities of challenges and advances in nanotoxicology research.

Immobilized carbon nanotubes as activators of cellular elements of blood in contact interaction

Background. The use of nanotechnology achievements in medicine opens up prospects for the development and improvement of means and methods of prevention and treatment of diseases of various origins. Carbon nanotubes (CNTs) are a product of modern nanotechnologies, and in addition to their unique physical and chemical properties, they are promising for practical applications in medicine. CNTs are one of the most popular (comparable only with silver and titanium dioxide nanoparticles) objects of nanotoxicological research. Data on the effect of CNTs on blood cells are contradictory, so additional studies are necessary. Objective. To assess the activation capabilities of immobilized carbon nanotubes by the rate of adhesion of blood cell elements to their surface in vitro. Design and methods. Hemocontact interaction was carried out in bench conditions using donor blood in rotational mode. Blood samples were taken before the start of the experiment and after 5, 20, 40 and 60 min. Changes in the indicators of cell blood populations using the hematology analyzer SySmex XT 1800i (26 parameters). 50 experiments were conducted. To analyze the activation functions, a speed-time adhesive profile was used. Results. The highest rates of activation of cellular elements of the blood were recorded in contact with multi-walled carbon nanotubes SiloMUNT. Conclusion. The results of the study can be further implemented in the procedure of low-volume hemoperfusion in clinical practice.

Review on microbially synthesized nanoparticles: a potent biocontrol agent against Aedes species of mosquito

Aedes aegypti is a principal vector of dengue, chikungunya and Zika illnesses worldwide. Because effective vaccinations or medications for the prevention and/or treatment for these illnesses are not available, vector management has been embraced as the primary method of reducing their transmission. The strategy that is often used for controlling Aedes populations is chemical insecticides; however, despite their efficiency, extensive usage of these pesticides has resulted in high operating costs, the establishment of resistant populations and undesirable non-target impacts. Therefore, the use of nanoparticles derived from multiple synthesis processes as new insecticides has recently attracted the interest of researchers. This study provides an overview of the current understanding concerning the method of action of nanoparticles against mosquitoes. Metal nanoparticles strongly influence antioxidant and detoxifying enzymes in insects, causing oxidative stress and cell death. These nanoparticles similarly inhibited acetylcholinesterase activity. Metal-based nanoparticles can potentially bind to S and P units in proteins and nucleic acids respectively resulting in decreased membrane permeability, organelle and enzyme denaturation which leads to cell death. Furthermore, they upregulate and downregulate critical insect genes, lower protein synthesis and gonadotrophin release, resulting in developmental and reproductive failure. This review critically examines insect nanotoxicology research trends and highlights the ecotoxicological effects of practical usage of nanoparticles as insecticides.

Lung Models to Evaluate Silver Nanoparticles' Toxicity and Their Impact on Human Health.

Nanomaterials (NMs) solve specific problems with remarkable results in several industrial and scientific areas. Among NMs, silver nanoparticles (AgNPs) have been extensively employed as drug carriers, medical diagnostics, energy harvesting devices, sensors, lubricants, and bioremediation. Notably, they have shown excellent antimicrobial, anticancer, and antiviral properties in the biomedical field. The literature analysis shows a selective cytotoxic effect on cancer cells compared to healthy cells, making its potential application in cancer treatment evident, increasing the need to study the potential risk of their use to environmental and human health. A large battery of toxicity models, both in vitro and in vivo, have been established to predict the harmful effects of incorporating AgNPs in these numerous areas or those produced due to involuntary exposure. However, these models often report contradictory results due to their lack of standardization, generating controversy and slowing the advances in nanotoxicology research, fundamentally by generalizing the biological response produced by the AgNP formulations. This review summarizes the last ten years’ reports concerning AgNPs’ toxicity in cellular respiratory system models (e.g., mono-culture models, co-cultures, 3D cultures, ex vivo and in vivo). In turn, more complex cellular models represent in a better way the physical and chemical barriers of the body; however, results should be used carefully so as not to be misleading. The main objective of this work is to highlight current models with the highest physiological relevance, identifying the opportunity areas of lung nanotoxicology and contributing to the establishment and strengthening of specific regulations regarding health and the environment.

Lysosomal impairment-mediated autophagy dysfunction responsible for the vascular endothelial apoptosis caused by silica nanoparticle via ROS/PARP1/AIF signaling pathway

Understanding the underlying interactions of nanoparticles (NPs) with cells is crucial to the nanotoxicological research. Evidences suggested lysosomes as a vital target upon the accumulation of internalized NPs, and lysosomal damage and autophagy dysfunction are emerging molecular mechanisms for NPs-elicited toxicity. Nevertheless, the interaction with lysosomes, ensuing adverse effects and the underlying mechanisms are still largely obscure, especially in NPs-induced vascular toxicity. In this study, silica nanoparticles (SiNPs) were utilized to explore the adverse effects on lysosome in vascular endothelial cells by using in vitro cultured human endothelial cells (HUVECs), and in-depth investigated the mechanisms involved. Consequently, the internalized SiNPs accumulated explicitly in the lysosomes, and caused lysosomal dysfunction, which were prominent on the increased lysosomal membrane permeability, decline in lysosomal quantity, destruction of acidic environment of lysosome, and also disruption of lysosomal enzymes activities, resulting in autophagy flux blockage and autophagy dysfunction. More importantly, mechanistic results revealed the SiNPs-caused lysosomal impairments and resultant autophagy dysfunction could promote oxidative stress, DNA damage and the eventual cell apoptosis activated by ROS/PARP1/AIF signaling pathway. These findings improved the understanding of SiNPs-induced vascular injury, and may provide novel information and warnings for SiNPs applications in the fields of nanomedicine.

NpSCOPE: A New Multimodal Instrument for In Situ Correlative Analysis of Nanoparticles.

Over the last few decades, nanoparticles have become a key element in a number of scientific and technological fields, spanning from materials science to life sciences. The characterization of nanoparticles or samples containing nanoparticles, in terms of morphology, chemical composition, and other parameters, typically involves investigations with various analytical tools, requiring complex workflows and extending the duration of such studies to several days or even weeks. Here, we report on the development of a new unique in situ correlative instrument, allowing us to answer questions about the shape, size, size distribution, and chemical composition of the nanoparticles using a single probe. Combining various microscopic and analytical capabilities in one single instrument allows a considerable increase in flexibility and a reduction in the duration of such complex investigations. The new instrument is based on focused ion beam microscopy technology using a gas field ion source as a key enabler and combining it with specifically developed secondary ion mass spectrometry and scanning transmission ion microscopy technology. We will present the underlying concept, the instrument and its main components, and proof-of-concept studies performed on this novel instrument. For this purpose, different pure titanium dioxide nanoparticle samples were investigated. Furthermore, the distribution and localization of the nanoparticles in biological model systems were studied. Our results demonstrate the performance and usefulness of the instrument for nanoparticle investigations, paving the way for a number of future applications, in particular, nanotoxicological research.

Copper Oxide Nanoparticle-Induced Acute Inflammatory Response and Injury in Murine Lung Is Ameliorated by Synthetic Secoisolariciresinol Diglucoside (LGM2605)

Metal-oxide nanoparticles (MO-NPs), such as the highly bioreactive copper-based nanoparticles (CuO-NPs), are widely used in manufacturing of hundreds of commercial products. Epidemiological studies correlated levels of nanoparticles in ambient air with a significant increase in lung disease. CuO-NPs, specifically, were among the most potent in a set of metal-oxides and carbons studied in parallel regarding DNA damage and cytotoxicity. Despite advances in nanotoxicology research and the characterization of their toxicity, the exact mechanism(s) of toxicity are yet to be defined. We identified chlorination toxicity as a damaging consequence of inflammation and myeloperoxidase (MPO) activation, resulting in macromolecular damage and cell damage/death. We hypothesized that the inhalation of CuO-NPs elicits an inflammatory response resulting in chlorination damage in cells and lung tissues. We further tested the protective action of LGM2605, a synthetic small molecule with known scavenging properties for reactive oxygen species (ROS), but most importantly, for active chlorine species (ACS) and an inhibitor of MPO. CuO-NPs (15 µg/bolus) were instilled intranasally in mice and the kinetics of the inflammatory response in lungs was evaluated 1, 3, and 7 days later. Evaluation of the protective action of LGM2605 was performed at 24 h post-challenge, which was selected as the peak acute inflammatory response to CuO-NP. LGM2605 was given daily via gavage to mice starting 2 days prior to the time of the insult (100 mg/kg). CuO-NPs induced a significant inflammatory influx, inflammasome-relevant cytokine release, and chlorination damage in mouse lungs, which was mitigated by the action of LGM2605. Preventive action of LGM2605 ameliorated the adverse effects of CuO-NP in lung.

Development and validation of a method for the weathering and detachment of representative nanomaterials from conventional silver-containing textiles

Nanotoxicology research commonly utilizes pristine nanomaterials for toxicity assessment, which may not be perfectly representative of what is released into environmental systems. The goal of the present study was to develop a method to simulate human weathering of silver-containing textiles. To achieve this goal the roles of physical and chemical stress on X-Static® containing athletic textiles were investigated and compared to data collected from human weathering experiments and literature. Chemical weathering methods (artificial sweat) were used independently and alongside physical weathering methods (3D printed stretching and abrasion instruments). Non-weathered control textiles were found to release 29 ± 11 mg Ag/kg of textile into wash water effluent (ICP-MS), with 16% being released as ionic silver (ICP-MS) and the rest as metallic nanomaterials, nanosheets, and particulates of varying size (SEM/XANES). Real and simulated human weathered textiles released similar amounts of total silver (67 ± 11 mg Ag/kg, 84 ± 13 mg Ag/kg respectively) with the silver released being composed of ionic (1.5%, 2%) and a mixture of metallic and chlorinated nanomaterials, nanosheets, and particulates. The method was shown to effectively detach environmentally representative silver materials from silver-containing textiles and can provide such materials for future studies on the assessment of their fate, transport, and toxicity.

Determination of the LD50 with the chick embryo chorioallantoic membrane (CAM) assay as a promising alternative in nanotoxicological evaluation

Toxicity tests in rodents are still considered a controversial topic concerning their ethical justifiability. The chick embryo chorioallantoic membrane (CAM) assay may offer a simple and inexpensive alternative. The CAM assay is easy to perform and has low bureaucratic hurdles. At the same time, the CAM assay allows the application of a broad variety of analytical methods in the field of nanotoxicological research. We evaluated the CAM assay as a methodology for the determination of nanotoxicity. Therefore we calculated the median lethal dose (LD50), performed in vivo microscopy and immunohistochemistry to identify organ-specific accumulation profiles, potential organ damage, and the kinetics of the in vivo circulation of the nanoparticles. Zinc oxide nanoparticles were intravascularly injected on day 10 of the egg development and showed an LD50 of 17.5 µM (1.4 µg/mLeggcontent). In comparison, the LD50 of equivalent amounts of Zn2+ was 4.6 µM (0.6 µg/mLeggcontent). Silica encapsulated ZnO@SiO2 nanoparticles conjugated with fluorescein circulated in the bloodstream for at least 24 h. Particles accumulated mostly in the liver and kidney. In immunohistochemical staining, organ damage was detected only in liver tissue after intravascular injection of zinc oxide nanoparticles in very high concentrations. Zinc oxide nanoparticles showed a different pharmacokinetic profile compared to Zn2+ ions. In conclusion, the CAM assay has proven to be a promising methodology for evaluating nanotoxicity and for the assessment of the in vivo accumulation profiles of nanoparticles. These findings may qualify the methodology for risk assessment of innovative nanotherapeutics in the future.

Commentary: Revisiting nanoparticle-assay interference: There's plenty of room at the bottom for misinterpretation.

Engineered nanomaterials (ENMs) are a diverse class of materials whose distinct properties make them desirable in a multitude of applications. The proliferation of nanotoxicology research has improved our understanding of ENM toxicity, but an under appreciation for their potential to interfere with biochemical assays has hampered progress in the field. The physicochemical properties of ENMs can promote their interaction with membranes or biomacromolecules (e.g. proteins, genomic material). This can influence the activity of enzymes used as biomarkers or as reagents in biochemical assay protocols, bind indicator dyes in cytotoxicity tests, and/or interfere with the cellular mechanisms controlling the uptake of such dyes. The spectral characteristics of some ENMs can cause interference with common assay chromophores, fluorophores, and radioisotope scintillation cocktails. Finally, the inherent chemical reactivity of some ENMs can short circuit assay mechanisms by directly oxidizing or reducing indicator dyes. These processes affect data quality and may lead to significant misinterpretations regarding ENM safety. We provide an overview of some ENM properties that facilitate assay interference, examples of interference and the erroneous conclusions that may result from it, and a number of general and specific recommendations for validating cellular and biochemical assay protocols in nanotoxicology studies.

Animal Biomedicine Controls Root Knot Disease in Lentil Callus Culture: Enriched Advanced Clinical Toxicology Socio Economy Science Technology Communication by Preventing 21st Century COVID-19 Like Pandemic Diseases

The economic pulse seeds, Lens esculentum L. Cv. ‘Asha’ root callus develop on Murashige and Skoog (MS)-media supplemented with 2 mg/1, 2,4-D (2,4-dichloro phenoxy acetic acid) and inoculated with Meloidogyne incognita larvae (65 ± 2 J2) in the culture tube to study their multiplication rate under sterilized condition in the tissue culture laboratory, and biomedicine-nematode extract (NE) prepared from M. incognita females, when applied at 1.3mg/culture tube to root callus of lentil, reduced nematode infestation of callus and improved callus growth. This animal biomedicine-NE is thought to induce defense-resistance in lentil root callus and may prevent 21st –century pandemics like virus diseases by boosting immunity, resisting toxic effects, and improved biomedicine, advanced in clinical toxicology, green-socio-economy, science technology, and communication application. The biomedicine-NE not only increase agriculture and crop production but also enable the development of a new-generation of nanotechnology-agrochemicals reducing negative-environmental-impacts and maintaining-crop-yields. And both; biomedicine-NE and pulses may itself focus on nanoformulation of agrochemicals and other nanotechnological interdisciplinary future nanotoxicology research and applications in agriculture, and interaction nanomaterials-NE with plants, their environment, and other organisms also.

In vivo percutaneous permeation of gold nanomaterials in consumer cosmetics: implication in dermal safety assessment of consumer nanoproducts

The increasing emergence of nano-cosmetics in the marketplace provokes safety concerns with respect to percutaneous permeation and toxicity of nanomaterials inside the human body. In this study, in vivo percutaneous permeation and dermal safety of cosmetic cream containing Au nanosheets and extracted Au nanosheets from cosmetic creams are investigated with guinea pigs. Quantitative percutaneous permeation data suggests that Au nanosheets in cosmetic creams permeate into the skin epidermis, dermis, and subcutaneous layer after 10 d cutaneous exposure, but cannot enter the systemic circulation. However, more Au nanosheets are accumulated in the skin and the permeation of Au nanosheets increased after embedded into the cream matrix. Synchrotron radiation X-ray fluorescence (SRXRF) imaging reveals that Au nanosheets in cosmetics penetrate mainly through hair follicles in a time-dependent manner. Cosmetic creams rather than extracted Au nanosheets decrease the cell viability of keratinocytes and slightly induce apoptosis/necrosis of keratinocytes and skin dermal fibroblasts. Intriguingly, the growth of hair is inhibited by the cosmetic cream and the extracted Au nanosheets revealed by HE staining and immunohistochemistry (IHC) assay. Altogether this study provides insights into the comprehensive understanding of percutaneous permeation and dermal safety of cosmetic creams containing Au nanosheets. This work provides reliable methods to study the skin permeation, biodistribution, and dermal safety of nano-cosmetics and reminds the community of the crucial need to combine the assays at molecular, cellular, and organ levels in nanotoxicology research.

The Influences of Aqueous Dispersion Media on the Cytotoxic Effect of Zinc Oxide Nanoparticles

Zinc oxide nanoparticles (ZnO-NPs) are widely utilized in many applications due to distinct physical and chemical characteristics. There are growing concerns that abundant use of ZnO-NPs can cause harm to humans and the environment. There is a substantial problem with reproducibility in nanotoxicology research due to the inherent properties of nanoparticles. Dispersion media are used for the preparation of nanoparticles. However, the physical and biological behaviors of ZnO-NPs in aqueous dispersion media are poorly understood. In this study, we investigated the effect of ZnO-NPs on the viability of SH-SY5Y cells. Our results showed that ZnO-NPs diluted from water-dispersed stock solution caused significant cell death at a much lower dose compared to their counterpart diluted from the phosphate-buffered saline (PBS)-dispersed stock solution. Electron microscopic data indicated that ZnO-NPs from the PBS-dispersed stock solution form much larger agglomerates compared to the one from the water-dispersed stock solution. From these data, we can conclude that the types of media used for particle dispersion impact the change in the physical property and cytotoxicity of ZnO-NPs.