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AbstractTitanium dioxide nanoparticles (TiO2NPs) as an emerging pollutant in aquatic environments can interact with metals reducing or enhancing their toxicity in these environments. This study examined and compared the toxic effects of mercury ions (Hg2+ ions) on immobilization percentage, fatty acid profile, and oxidative stress of Artemia salina nauplii, individually (Hg) and simultaneously in the presence of 0.10 mg.L−1 (Hg-0.1TiO2NPs) and 1.00 mg.L−1 TiO2NPs (Hg-1TiO2NPs). The interaction between Hg2+ ions and TiO2NPs was evaluated using DLS and AAS-VGA. Simultaneous exposures exhibited an unexpected dual effect on A. salina nauplii. A synergistic effect was observed in Hg-0.1TiO2NPs, while increasing the TiO2NPs concentration in Hg-1TiO2NPs prevented the synergy of the mixture compounds offering an antagonistic effect on nauplii. This dual effect was assigned to a greater number of available active sites and agglomeration of TiO2NPs at higher concentrations. Oxidative stress and lipid peroxidation induced by Hg were diminished in Hg-1TiO2NPs in line with the immobilization results. In Hg, total amounts of saturated fatty acids (∑SFA) increased while total monounsaturated (∑MUFA) and total polyunsaturated (∑PUFA) ones decreased compared with the control. However, they showed no significant change considering the control in Hg-1TiO2NPs, again confirming the antagonistic effect on nauplii. The unsaturated to saturated fatty acids ratio decreased in both Hg and Hg-1TiO2NPs compared with the control, however, this reduction in Hg-1TiO2NPs was lower than in Hg. The present results emphasized getting a more comprehensive understanding of how TiO2NPs impact the bioavailability and toxicity of co-contaminants through their combined effects and interactions. [ABSTRACT FROM AUTHOR]

The use of nanoparticles (NPs) in treatment of diseases have increased exponentially recently, giving rise to the science of nanomedicine. The safety of these NPs in humans has also led to the science of nanotoxicology. Due to a dearth of both readily available models and precise bio-dispersion characterization techniques, nanotoxicological research has obviously been constrained. However, the ensuing years were notable for the emergence of improved synthesis methods and characterization tools. Major advances have been made in linking certain physical variables, paralleling improvements in characterization size, shape, or coating factors to the resulting physiological reactions. Although significant progress has been a contribution to the development of nanotoxicology, however, it faces numerous difficulties and technical constraints distinct from those of conventional toxicological assessment as it attempts to improve the therapeutic effects of medicines. Determining thorough characterization standards, standardizing dosimetry, assessing the kinetics of ions dissolving and enhancing the accuracy of in vitro-in vivo correlation efficiency, also defining restrictions on exposure protection are some of the most important and pressing concerns. This article will explore the past advancement and potential prospects of nanotoxicology, standard models, emphasizing significant findings from earlier studies and examining current challenges, giving insight on the way forward. [ABSTRACT FROM AUTHOR]

Background: Inorganic ultraviolet filters such as titanium dioxide nanoparticles are frequently used in sunscreens. Numerous toxicological studies in vitro and in vivo have been conducted using pristine standard reference nanomaterials of these inorganic filters. While convenient, this approach is not realistic because the complex environment of sunscreen formulations could change the physicochemical properties of the nanoparticles and lead to vastly different toxicological outcomes. Therefore, this study focused on characterizing nanoparticles extracted from commercial sunscreen and evaluating the associated toxicological impacts upon exposure to human keratinocytes and human skin explants. Results: Titanium dioxide nanoparticles were extracted from commercial sunscreens and thoroughly characterized. The identity of the associated molecular corona on the extracted nanoparticles was also evaluated. Cell metabolic and proliferation profiles, mitochondrial superoxide activity, reactive oxygen species levels, and genotoxicity induced through exposure to the nanoparticles were studied in vitro using a human keratinocyte cell line. The cell response was significantly different after treatment with pristine nanoparticles compared to corresponding sunscreen-extracted nanoparticles. Pristine spherical nanoparticles resulted in more pronounced toxicity in 2D cultured keratinocytes compared to extracted nanoparticles but did not impact wound-edge migration significantly in 3D ex vivo human skin explant models. Additionally, extracted rod-shaped nanoparticles had greater toxic impacts in keratinocytes in vitro and retarded wound-edge migration in the ex vivo model compared to the extracted spherical nanoparticles. Nevertheless, these heightened cell responses were not associated with any increase in phosphorylated γH2AX (which is indicative of DNA damage) both in vitro and ex vivo. Conclusions: This study shows the feasibility of extracting nanoparticles from personal care products such as sunscreens to obtain relevant forms to model real-life exposure scenarios. Overall, sunscreen-extracted nanoparticles were found to be less toxic compared to pristine equivalents but retarded wound-edge migration more significantly. Skin explant cultures provide a more realistic alternative to monolayer cell cultures, although the differential outcomes between the models need more in-depth evaluation. [ABSTRACT FROM AUTHOR]

Our research group previously studied the effectiveness of lipid-core nanocapsules (LNC) containing simvastatin (SV-LNC) in treating cognitive impairment in rats. While our results were promising, we needed to evaluate the potential toxicity of the nanoparticles themselves. This study aimed to compare the biochemical and hematological parameters of adult Wistar rats receiving LNC or SV-LNC to those receiving low doses of simvastatin crystals dispersed in a saline solution over 45 days. We discovered that LNC and SV-LNC, which are both nanometers in size with low polydispersity index, negative zeta potential, and high SV encapsulation efficacy, were not more toxic than SV crystals based on various biochemical markers of hepatic, pancreatic, renal, mineral, bony, alkaline phosphatase, glucose, and uric acid damage. Furthermore, LNC exhibited no toxicity for hematological parameters, including red and white blood cell counts. Based on this animal model of toxicological study, our findings suggest that long-term administration of LNC is a safe and promising nanocarrier. [ABSTRACT FROM AUTHOR]

The Turkevich method was optimized to prepare gold nanoparticles (AuNP) stabilized by polyethyleneglycol (PEG) for µCT. Using various independent modalities, we thoroughly characterized the optimized PEG-AuNPs. Here, we show that PEG-AuNPs are retained in the blood and provide a high contrast in the high-resolution µCT imaging of blood vessels and inner organs. The biodistribution is characterized by prolonged circulation in the blood and accumulation in the liver, spleen and skin. The accumulation of AuNP in the skin resulted in the blue discoloration of eyes and the whole skin. In vitro experiments using a leukemic monocyte THP-1 cell line model expressing high levels of NLRP3 demonstrated that the NLRP3inflammasome was not activated by PEG AuNP. Over 9 months, the mice were scanned by µCT and were in good health. Scans in mice using PEG-stabilized AuNPs in this study were sharper, with a higher contrast, when compared to a commercial contrasting agent at the same dose. The PEG-AuNPs were morphologically and chemically stable for at least two years when stored in the refrigerator. [ABSTRACT FROM AUTHOR]

This review paper focuses on the joint toxicity and interaction of carbon-based nanomaterials (CNMs) with co-existing pollutants in aquatic environments. It explores the potential harmful effects of chemical mixtures with CNMs on aquatic organisms, emphasizing the importance of scientific modeling to predict mixed toxic effects. The study involved a systematic literature review to gather information on the joint toxicity and interaction between CNMs and various co-contaminants in aquatic settings. A total of 53 publications were chosen and analyzed, categorizing the studies based on the tested CNMs, types of co-contaminants, and the used species. Common test models included fish and microalgae, with zebrafish being the most studied species. The review underscores the necessity of conducting mixture toxicity testing to assess whether the combined effects of CNMs and co-existing pollutants are additive, synergistic, or antagonistic. The development of in silico models based on the solid foundation of research data represents the best opportunity for joint toxicity prediction, eliminating the need for a great quantity of experimental studies. [ABSTRACT FROM AUTHOR]

Abstract Background Inorganic ultraviolet filters such as titanium dioxide nanoparticles are frequently used in sunscreens. Numerous toxicological studies in vitro and in vivo have been conducted using pristine standard reference nanomaterials of these inorganic filters. While convenient, this approach is not realistic because the complex environment of sunscreen formulations could change the physicochemical properties of the nanoparticles and lead to vastly different toxicological outcomes. Therefore, this study focused on characterizing nanoparticles extracted from commercial sunscreen and evaluating the associated toxicological impacts upon exposure to human keratinocytes and human skin explants. Results Titanium dioxide nanoparticles were extracted from commercial sunscreens and thoroughly characterized. The identity of the associated molecular corona on the extracted nanoparticles was also evaluated. Cell metabolic and proliferation profiles, mitochondrial superoxide activity, reactive oxygen species levels, and genotoxicity induced through exposure to the nanoparticles were studied in vitro using a human keratinocyte cell line. The cell response was significantly different after treatment with pristine nanoparticles compared to corresponding sunscreen-extracted nanoparticles. Pristine spherical nanoparticles resulted in more pronounced toxicity in 2D cultured keratinocytes compared to extracted nanoparticles but did not impact wound-edge migration significantly in 3D ex vivo human skin explant models. Additionally, extracted rod-shaped nanoparticles had greater toxic impacts in keratinocytes in vitro and retarded wound-edge migration in the ex vivo model compared to the extracted spherical nanoparticles. Nevertheless, these heightened cell responses were not associated with any increase in phosphorylated γH2AX (which is indicative of DNA damage) both in vitro and ex vivo. Conclusions This study shows the feasibility of extracting nanoparticles from personal care products such as sunscreens to obtain relevant forms to model real-life exposure scenarios. Overall, sunscreen-extracted nanoparticles were found to be less toxic compared to pristine equivalents but retarded wound-edge migration more significantly. Skin explant cultures provide a more realistic alternative to monolayer cell cultures, although the differential outcomes between the models need more in-depth evaluation.

Abstract The same elements can yield disparate nanoproducts that may elicit different harmful effects in cells and organisms. This study aimed to compare the effects of copper (Cu NPs) and copper oxide (CuO NPs) nanoparticles and Cu2+ (from CuSO4) on the physico-biochemical variables of rainbow trout spermatozoa. The cell death assay, along with the activation of caspases 8 and 9, the level of reactive oxygen species (ROS), and the percentage of cells exhibiting a high mitochondrial membrane potential (MMP) were quantified over 24-hour incubation. Interestingly, during exposure, all copper products induced cell apoptosis. However, Cu NPs had a stronger effect than CuO NPs, while the impact of the Cu in ionic form was found to be between the other two compounds. The extrinsic and intrinsic apoptotic pathways were activated, as evidenced by the activation of caspases 8 and 9. Initially, caspase activation increased without a corresponding decrease in MMPs but prolonged exposure resulted in a significant decrease in MMP levels. In all treated cells, the ROS levels increased over time. Further studies are needed to confirm the lower CuO NPs’ toxicity compared to Cu NPs because their effect on cells also depends on many other parameters such as size or shape.

The field of nanotechnology has experienced exponential growth, with the unique properties of nanomaterials (NMs) being employed to enhance a wide range of products across diverse industrial sectors. This study examines the toxicity of metal- and carbon-based NMs, with a particular focus on titanium dioxide (TiO2), zinc oxide (ZnO), silica (SiO2), cerium oxide (CeO2), silver (Ag), and multi-walled carbon nanotubes (MWCNTs). The potential health risks associated with increased human exposure to these NMs and their effect on the respiratory, gastrointestinal, dermal, and immune systems were evaluated using in vitro assays. Physicochemical characterisation of the NMs was carried out, and in vitro assays were performed to assess the cytotoxicity, genotoxicity, reactive oxygen species (ROS) production, apoptosis/necrosis, and inflammation in cell lines representative of the systems evaluated (3T3, Caco-2, HepG2, A549, and THP-1 cell lines). The results obtained show that 3T3 and A549 cells exhibit high cytotoxicity and ROS production after exposure to ZnO NMs. Caco-2 and HepG2 cell lines show cytotoxicity when exposed to ZnO and Ag NMs and oxidative stress induced by SiO2 and MWCNTs. THP-1 cell line shows increased cytotoxicity and a pro-inflammatory response upon exposure to SiO2. This study emphasises the importance of conducting comprehensive toxicological assessments of NMs given their physicochemical interactions with biological systems. Therefore, it is of key importance to develop robust and specific methodologies for the assessment of their potential health risks. [ABSTRACT FROM AUTHOR]

In this study, nitrogen‐doped carbon nanodots (N‐CNDs) were synthesized from Citrus reticulata using microwave‐assisted process and material's genotoxic effects were investigated in Daphnia magna. Morphological size and shape variations of the synthesized N‐CNDs were evaluated by using zetasizer and transmission electron microscope. Acute/chronic toxicity experiments were performed using method by OECD (Organization for Economic Cooperation and Development) 202–212 guidelines. Daphnia magna was subjected to the N‐CNDs produced from Citrus reticulata at the different concentrations ranging between 0.04 and0.24 mg tangerine equivalent N‐CND/mL for 96 h at 20 °C. After 96 h, the LC50 (lethal concentration‐ at which 50% of cells) value of N‐CNDs was determined to be 0.1 mg equivalent N‐CND/mL using probit analysis. Based on toxicity levels determined by EU‐Directive 93/67/EEC, N‐CNDs are classified in the nontoxic category. The toxicological assessments of sublethal concentrations of N‐CNDs demonstrated that 0.013 mg tangerine equivalent N‐CND/mL dose group exhibited a similar profile to the control group, indicating its safety. Although the DNA damage frequency of the 0.03 and 0.06 mg equivalent N‐CND/mL dose groups was found to be higher than control group, these levels were observed almost 70% lower than the DNA damage frequency found in the mutagenic group/positive group. [ABSTRACT FROM AUTHOR]

Nanotechnology is emerging as a promising tool to enhance traditional cancer treatments due to rising chemotherapy resistance and the severe side effects of toxic drugs. Silver nanoparticles (AgNPs) are widely acknowledged for their antimicrobial and antiproliferative properties. Given these AgNP characteristics, this research conducts a comprehensive nanotoxicological assessment of strategic combinations involving AgNPs (68 nm) commercial formulation and tamoxifen on MCF‐7 and MDA‐MB‐231 breast tumor cells. Utilizing CompuSyn software, the combination index was determined, revealing a synergistic cytotoxic and antiproliferative effect in AgNPs and tamoxifen combinations (CI < 0.97). Furthermore, this combination impaired cell migration (the scratch zone expanded by over 270%) and significantly increased reactive oxygen species production (up to 96% for MDA‐MB‐231 and 52% for MCF‐7 cells). Surprisingly, the genotoxic effect of these mixtures was minimal (below the allowable genotoxicity index of 1.5). Additionally, both breast tumor cell lines exhibited increased proapoptotic and oxidative stress gene expression following the combined treatment. The internalization of AgNPs into breast cancer cells was observed, enhancing their synergistic antiproliferative effect when combined with tamoxifen. These findings suggest the potential of combining AgNPs with chemotherapeutic agents for innovative studies in oncology therapy. Highlights: Small silver nanoparticles (AgNP) and tamoxifen mix is no‐genotoxic and boosts synergistic cytotoxicity.AgNPs and tamoxifen combo overexpress proapoptotic and oxidative stress genes.Tamoxifen's antiproliferative effect ramps up via AgNPs inducing oxidative stress.AgNPs internalized by breast cancer cells heighten antiproliferative effect. [ABSTRACT FROM AUTHOR]

The same elements can yield disparate nanoproducts that may elicit different harmful effects in cells and organisms. This study aimed to compare the effects of copper (Cu NPs) and copper oxide (CuO NPs) nanoparticles and Cu2+ (from CuSO4) on the physico-biochemical variables of rainbow trout spermatozoa. The cell death assay, along with the activation of caspases 8 and 9, the level of reactive oxygen species (ROS), and the percentage of cells exhibiting a high mitochondrial membrane potential (MMP) were quantified over 24-hour incubation. Interestingly, during exposure, all copper products induced cell apoptosis. However, Cu NPs had a stronger effect than CuO NPs, while the impact of the Cu in ionic form was found to be between the other two compounds. The extrinsic and intrinsic apoptotic pathways were activated, as evidenced by the activation of caspases 8 and 9. Initially, caspase activation increased without a corresponding decrease in MMPs but prolonged exposure resulted in a significant decrease in MMP levels. In all treated cells, the ROS levels increased over time. Further studies are needed to confirm the lower CuO NPs’ toxicity compared to Cu NPs because their effect on cells also depends on many other parameters such as size or shape. [ABSTRACT FROM AUTHOR]

In recent years, advances in nanotechnology have significantly influenced electronics manufacturing, industrial processes, and medical research. Various industries have seen a surge in the use of nanomaterials. However, several researchers have raised the alarm about the toxicological nature of nanomaterials, which appear to be quite different from their crude forms. This altered nature can be attributed to their unique physicochemical profile. They can adversely affect human health and the environment. Nanomaterials that have been released into the environment tend to accumulate over time and can cause a significant impact on the ecosystem and organisms with adverse health effects. Increased use of nanoparticles has led to increased human exposure in their daily lives, making them more vulnerable to nanoparticle toxicity. Because of their small size, nanomaterials can readily cross biological membranes and enter cells, tissues, and organs. Therefore, the effect of nanomaterials on the human environment is of particular concern. The toxicological effects of nanomaterials and their mechanisms of action are being researched worldwide. Technological advances also support monitoring new nanomaterials marketed for industrial and household purposes. It is a challenging area because of the exceptional physicochemical properties of nanomaterials. This updated review focuses on the diverse toxicological perspective of nanomaterials. We have discussed the use of different types of nanoparticles and their physiochemical properties responsible for toxicity, routes of exposure, bio-distribution, and mechanism of toxicity. The review also includes various in vivo and in vitro methods of assessing the toxicity of nanomaterials. Finally, this review will provide a detailed insight into nano material-induced toxicological response, which can be beneficial in designing safe and effective nanoparticles. [ABSTRACT FROM AUTHOR]

IntroductionCurrent in vitro intestinal models lack the mechanical forces present in the physiological environment, limiting their reliability for nanotoxicology studies. Here, we developed an enhanced Caco-2/HT29-MTX-E12 co-culture model incorporating orbital mechanical stimulation to better replicate intestinal conditions and investigate nanoparticle interactions.MethodsWe established co-cultures under static and dynamic conditions, evaluating their development through multiple approaches including barrier integrity measurements, gene expression analysis, and confocal microscopy. We introduced novel quantitative analysis of dome formation as a differentiation marker and demonstrated the model application by investigating cellular responses to titanium dioxide (TiO₂) nanoparticles in a digested food matrix.ResultsDynamic conditions accelerated epithelial differentiation, achieving functional barrier properties by day 14 rather than day 21, with enhanced mucin production and more organized three-dimensional structure. Mechanical stimulation selectively promoted goblet cell differentiation without affecting general epithelial markers. The optimized model successfully detected concentration-dependent oxidative stress responses to TiO₂ exposure, revealing cellular dysfunction preceding membrane damage.DiscussionThis improved co-culture system provides a better physiological platform for nanotoxicology studies. By incorporating mechanical forces, each cell type exhibits more representative behavior, creating a more realistic experimental setup. The model bridges the gap between simple monocultures and complex 3D systems, offering a practical approach for investigating nanoparticle-epithelium interactions in a food-relevant context.

The extensive production and use of plastics in recent decades has led to environmental pollution. It has been discovered that plastic microparticles (MPs) and nanoparticles (NPs), formed under the influence of physical forces, can pose a significant health risk. Increasing evidence indicates that NPs can have various toxic effects, including oxidative stress and cell death. However, the mechanisms underlying their toxicity are still under investigation. In this study, we examined whether polystyrene nanoparticles (PS-NPs) are internalized in primary astrocytes. We tracked their intracellular fate and search for potential interference with the intercellular communication pathway mediated by extracellular vesicles (EVs). Primary astrocyte cultures were exposed to fluorescent PS-NPs at concentrations of 0.5, 1, 25 and 50 µg/mL for 24, 48 and 72 hours. Based on electron microscopic analysis and confocal imaging, we determined that PS-NPs are internalized in astrocytes and accumulate in the cytoplasm in a concentration-dependent manner, localizing to endosomal-lysosomal system. Astrocytes exposed to PS-NPs form EVs containing encapsulated PS-NPs, which are released into the culture medium after 72 h of exposure and can be transferred via this route to other cells. As shown by proteomic analysis, PS-NPs affects the composition of the protein cargo of released EVs by decreasing the representation of proteins such as CD47, CSTB and CNDP2. Intercellular transport of PS-NPs in primary astrocytes is mediated by EVs system. EV-mediated release of PS-NPs may alleviate their toxicity in a single astrocyte but may also contribute to the spread of their toxic effect to neighbouring astrocytes. Exposure to PS-NPs interferes with the mechanism of protein sorting, thereby potentially influencing the EV-mediated cell-cell communication pathway.

Synthetically produced silicon dioxide used as a food additive exhibits nanoparticle size and shape during the early stages of manufacturing. Even when processed into food products, these nanoparticles are detected. Although processing food ingredients into nanoparticles can improve absorption rates or enhance texture, there are concerns about the specific biological effects of nanoparticles. In this study, three types of silica particles, including nanosized particles, were repetitively administered to the stomach using a gastric tube or exposed to a single injection into the submucosal layer of the stomach. Macroscopic and microscopic examinations did not reveal acute toxicity. However, when silica particles were administered to the stomach during the healing and regeneration process of gastric ulcers (induced by injecting the alkylating agent of N-Methyl-N′-Nitro-N-Nitrosoguanidine into the submucosal layer), silica particles with a diameter of 70 nm (SiNPs-70) delayed regeneration more strongly than microsized silica particles with diameters of 300 nm or 1000 nm (SiMPs-300, -1000). Furthermore, fibrosis for tissue regeneration spread throughout the entire mucosa of the stomach, resulting in hypertrophic gastritis-like symptoms. The frequency of this symptom was over 50% with SiNPs-70, 20% with SiMPs-300, and 0% with SiMPs-1000. Although the silica particles used in this study differ from actual samples found in food, the impact of particle size, particularly the effects unique to nanosize, was identified as toxicity in the stomach healing process. [ABSTRACT FROM AUTHOR]

Many products contain silver nanoparticles, which are adsorbed by living organisms and then go through biological barriers. In particular, penetration of silver nanoparticles through the placental barrier is likely to damage the offspring. Here, we review hazards of silver nanoparticles with focus on exposure during pregnancy, toxicokinetics at maternal and fetal layers, ex vivo and in vivo placenta transfer models, and factors affecting the transfer. Exposure occurs by oral uptake, inhalation, dermal contact, and systemic administration. Toxicokinetics include absorption, distribution in tissues, metabolism and excretion. The accumulation efficiency is primarily influenced by the mode of exposure. Injection exhibits the highest bioavailability, followed by inhalation and oral uptake. Particles within the range of tens of nanometers are capable of crossing the placenta, according to an ex vivo placental perfusion model. In contrast, larger particles in the range of hundreds of nanometers are expelled outside. Due to the size restriction of the trophoblast channel, which typically ranges from 15 to 25 nm, it is possible for silver nanoparticles with an average size of around 20 nm to passively enter the placenta through the pericellular pathway, such as diffusion. On the other hand, larger silver nanoparticles may be delivered to the placenta through endocytosis, which can occur via phagocytosis, receptor-mediated or independent mechanisms. [ABSTRACT FROM AUTHOR]

Topical infection affects nearly one-third of the world's population; it may result from poor sanitation, hygienic conditions and crowded living and working conditions that accelerate the spread of topical infectious diseases. The problems associated with the anti-infective agents are drug resistance and long-term therapy. Secondary metabolites are obtained from plants, microorganisms and animals, but they are metabolized inside the human body. The integration of nanotechnology into secondary metabolites is gaining attention due to their interaction at the subatomic and skin-tissue levels. Hydrogel, liposomes, lipidic nanoparticles, polymeric nanoparticles and metallic nanoparticles are the most suitable carriers for secondary metabolite delivery. Therefore, the present review article extensively discusses the topical applications of nanomedicines for the effective delivery of secondary metabolites. Executive summary Plant secondary metabolites Plants possess several secondary metabolites demonstrating antimicrobial properties, including flavonoids, alkaloids, tannins and terpenoids. Animal secondary metabolites Only a handful of secondary metabolites that have antimicrobial properties have been identified from animal sources. To date, no nanoformulation has been developed from animal secondary metabolites to treat topical infections. This field requires more scientific investigation to gain a better understanding of animal secondary metabolites and their delivery for topical applications. Microorganism secondary metabolites Some researchers have reported that microbial pigments (e.g., melanin, carotenoids, violacein, quinones, flavonoids and manascins), which are the secondary metabolites of microorganisms, show good antimicrobial properties. Skin barrier function The skin has a complex structure and diverse biophysical properties that modulate its barrier function. Specifically, the stratum corneum layer creates a barrier that facilitates the permeation of hydrophobic molecules more efficiently than hydrophilic molecules. However, the hydrophilic bilayer region hinders highly hydrophobic compounds. Environmental & individual factors Drug delivery through the skin is heavily influenced by environmental factors (temperature, oxygen level, humidity and light) and individual factors (sex, age, skin anatomy, hormonal balance and humidity). Drug stability & compatibility Developing strategies to enter the skin and efficiently deliver therapeutics is a significant area of research. Drugs quickly and directly go through the skin through the intracellular route. This method is difficult, however, because the particle must get past the water- and fat-absorbing parts of skin cells. Moreover, the drug must be stable and compatible with the skin and the delivery system. Nanocarriers Different kinds of nanocarriers, such as liposomes, microemulsions, hydrogels, solid lipids and polymeric nanoparticles, are used to deliver secondary metabolites such as curcumin, quercetin, berberine and eugenol into the skin. It has several advantages: controlled release, site-specific delivery, enhanced bioavailability, reduced toxicity, and increased solubility and stability. Nanocarrier barrier Several barriers impede the seamless integration of this technology into practical applications. Nanoparticle synthesis and formulation are difficult because one must design and optimize these carriers carefully to encapsulate and protect secondary metabolites while also ensuring controlled release. Nanotoxicity The toxicity of nanocarriers is influenced by composition, size, shape, surface charge, stability and biodegradability. [ABSTRACT FROM AUTHOR]

Heart failure represents a primary cause of hospitalization and mortality in both developed and developing countries, often necessitating heart transplantation as the only viable recovery path. Despite advances in transplantation medicine, organ rejection remains a significant post-operative challenge, traditionally monitored through invasive endomyocardial biopsies (EMB). This study introduces a rapid prototyping approach to organ rejection monitoring via a sensor-integrated flexible patch, employing electrical impedance spectroscopy (EIS) for the non-invasive, continuous assessment of resistive and capacitive changes indicative of tissue rejection processes. Utilizing titanium-dioxide-coated electrodes for contactless impedance sensing, this method aims to mitigate the limitations associated with EMB, including procedural risks and the psychological burden on patients. The biosensor's design features, including electrode passivation and three-dimensional microelectrode protrusions, facilitate effective monitoring of cardiac rejection by aligning with the heart's curvature and responding to muscle contractions. Evaluation of sensor performance utilized SPICE simulations, scanning electron microscopy, and cyclic voltammetry, alongside experimental validation using chicken heart tissue to simulate healthy and rejected states. The study highlights the potential of EIS in reducing the need for invasive biopsy procedures and offering a promising avenue for early detection and monitoring of organ rejection, with implications for patient care and healthcare resource utilization. [ABSTRACT FROM AUTHOR]

Micro- and nanoplastics have emerged as pervasive environmental pollutants with potential ecotoxicological impacts on various organisms, including the model organism Drosophila melanogaster. Here we comprehensively synthesize current research on the adverse effects of micro- and nanoplastics on Drosophila, highlighting key findings and identifying gaps in the literature. Micro- and nanoplastics can lead to physical damage, oxidative stress, inflammation, genotoxicity, epigenetic changes, apoptosis, and necrosis in Drosophila. Exposure to plastic debris affects nutrient absorption, energy metabolism, and reproductive health, often in a sex-specific manner. For instance, male flies are generally more susceptible to the toxic effects of polystyrene microplastics than female flies, showing greater mortality and metabolic disruptions. Furthermore, the combined exposure of plastics with heavy metals can exacerbate toxic effects, leading to enhanced oxidative stress, genotoxicity, and gut damage. While antagonistic effects have been identified particularly with silver compounds, where polystyrene microplastics reduce the bioavailability and toxicity of silver. The adverse effects of plastic particles on Drosophila depend on size, with smaller particles penetrating deeper into tissues and eliciting stronger toxic responses. The chemical composition of the plastics and the presence of additives also play crucial roles in determining toxicity levels. Chronic exposure to low levels can be as harmful as acute high-dose exposure, highlighting the need for comprehensive, long-term studies to fully understand the ecological and biological impacts of plastic pollution.

The widespread use of nanomaterials in agriculture may introduce multiple engineered nanoparticles (ENPs) into the environment, posing a combined risk to crops. However, the precise molecular mechanisms explaining how plant tissues respond to mixtures of individual ENPs remain unclear, despite indications that their combined toxicity differs from the summed toxicity of the individual ENPs. Here, we used a variety of methods including physicochemical, biochemical, and transcriptional analyses to examine the combined effects of graphene nanoplatelets (GNPs) and titanium dioxide nanoparticles (TiO2 NPs) on hydroponically exposed lettuce (Lactuca sativa) seedlings. Results indicated that the presence of GNPs facilitated the accumulation of Ti as TiO2 NPs in the seedling roots. Combined exposure to GNPs and TiO2 NPs caused less severe oxidative damage in the roots compared to individual exposures. Yet, GNPs and TiO2 NPs alone and in combination did not cause oxidative damage in the shoots. RNA sequencing data showed that the mixture of GNPs and TiO2 NPs led to a higher number of differentially expressed genes (DEGs) in the seedlings compared to exposure to the individual ENPs. Moreover, the majority of the DEGs encoding superoxide dismutase displayed heightened expression levels in the seedlings exposed to the combination of GNPs and TiO2 NPs. The level of gene ontology (GO) enrichment in the seedlings exposed to the mixture of GNPs and TiO2 NPs was found to be greater than the level of GO enrichment observed after exposure to isolated GNPs or TiO2 NPs. Furthermore, the signaling pathways, specifically the “MAPK signaling pathway-plant” and “phenylpropanoid biosynthesis,” exhibited a close association with oxidative stress. This study has provided valuable insights into the molecular mechanisms underlying plant resistance against multiple ENPs.

Lactation women, a highly concerned demographic in society, face health risks that deserve attention. Zinc oxide nanoparticles (ZnO NPs) are widely utilized in food and daily products due to their excellent physicochemical properties, leading to the potential exposure of lactating women to ZnO NPs. Hence, assessing the potential risks associated with ZnO NP exposure during lactation is critical. While studies have confirmed that exposure to ZnO NPs during lactation can induce toxic responses in multiple organs through blood circulation, the effects of lactational exposure on mammary tissue remain unclear. This research investigated the impairment of mammary tissue induced by ZnO NPs and its potential mechanisms. Through administering multiple injections of ZnO NPs into the tail vein of lactating ICR mice, our study revealed that ZnO NPs can deposit in the mammary tissues, downregulating key components of mammary epithelial barrier such as ZO-1, occludin, and claudin-3. In vivo, we also found that ZnO NPs can simultaneously induce apoptosis, necroptosis, and pyroptosis, called PANoptosis. Additionally, using EpH4-Ev cells to simulate an in vitro mammary epithelial barrier model, we observed that ZnO NPs effectively disrupted the integrity of mammary epithelial barrier and induced PANoptosis. Furthermore, we confirmed that PANoptosis was responsible for the mammary epithelial barrier disruption induced by ZnO NPs. Moreover, we identified that ZBP1 was the primary mechanism of ZnO NPs inducing PANoptosis. These discoveries are designed to enhance our comprehension of the mechanisms underlying mammary epithelial barrier disruption caused by ZnO NPs, and we aim to highlight the potential hazards associated with daily usage and therapeutic exposure to ZnO NPs during lactation.

In recent years, advances in nanotechnology have significantly influenced electronics manufacturing, industrial processes, and medical research. Various industries have seen a surge in the use of nanomaterials. However, several researchers have raised the alarm about the toxicological nature of nanomaterials, which appear to be quite different from their crude forms. This altered nature can be attributed to their unique physicochemical profile. They can adversely affect human health and the environment. Nanomaterials that have been released into the environment tend to accumulate over time and can cause a significant impact on the ecosystem and organisms with adverse health effects. Increased use of nanoparticles has led to increased human exposure in their daily lives, making them more vulnerable to nanoparticle toxicity. Because of their small size, nanomaterials can readily cross biological membranes and enter cells, tissues, and organs. Therefore, the effect of nanomaterials on the human environment is of particular concern. The toxicological effects of nanomaterials and their mechanisms of action are being researched worldwide. Technological advances also support monitoring new nanomaterials marketed for industrial and household purposes. It is a challenging area because of the exceptional physicochemical properties of nanomaterials. This updated review focuses on the diverse toxicological perspective of nanomaterials. We have discussed the use of different types of nanoparticles and their physiochemical properties responsible for toxicity, routes of exposure, bio-distribution, and mechanism of toxicity. The review also includes various in vivo and in vitro methods of assessing the toxicity of nanomaterials. Finally, this review will provide a detailed insight into nano material-induced toxicological response, which can be beneficial in designing safe and effective nanoparticles.

Abstract Iron oxide nanoparticles (FeO-NPs) are widely used in scientific and technological fields. Environmental concerns have been raised about residual FeO-NPs levels as their toxicity and bioaccumulative potential are not well understood. Oreochromis niloticus were exposed to nanoparticles of γ-Fe2O3 and Fe3O4. Micro-CT 3D image and grayscale graphic assessments revealed the accumulation of radiopaque material in the digestive tract of fish exposed to FeO-NPs. Histological analysis showed the presence of such NPs in the hepatopancreas, gills, kidneys, and muscles. No genotoxicity occurred, through micronucleus test and comet assay in peripheral erythrocytes. Body clearance was confirmed by iron-content reduction in organisms exposed to FeO-NPs after recovery period. No tissue injuries were observed in the exposed animals which may be attributed to the absence or low toxicity of iron oxide nanoparticles under the study conditions. O. niloticus showed tolerance to sublethal exposures to FeO-NPs.

Abstract Modern imaging strategies are paramount to studying living systems such as cells, bacteria, and fungi and their response to pathogens, toxicants, and nanomaterials (NMs) as modulated by exposure and environmental factors. The need to understand the processes and mechanisms of damage, healing, and cell survivability of living systems continues to motivate the development of alternative imaging strategies. Of particular interest is the use of label-free techniques (microscopy procedures that do not require sample staining) that minimize interference of biological processes by foreign marking substances and reduce intense light exposure and potential photo-toxicity effects. This review focuses on the synergic capabilities of atomic force microscopy (AFM) as a well-developed and robust imaging strategy with demonstrated applications to unravel intimate details in biomedical applications, with the label-free, fast, and enduring Holotomographic Microscopy (HTM) strategy. HTM is a technique that combines holography and tomography using a low intensity continuous illumination laser to investigate (quantitatively and non-invasively) cells, microorganisms, and thin tissue by generating three-dimensional (3D) images and monitoring in real-time inner morphological changes. We first review the operating principles that form the basis for the complementary details provided by these techniques regarding the surface and internal information provided by HTM and AFM, which are essential and complimentary for the development of several biomedical areas studying the interaction mechanisms of NMs with living organisms. First, AFM can provide superb resolution on surface morphology and biomechanical characterization. Second, the quantitative phase capabilities of HTM enable superb modeling and quantification of the volume, surface area, protein content, and mass density of the main components of cells and microorganisms, including the morphology of cells in microbiological systems. These capabilities result from directly quantifying refractive index changes without requiring fluorescent markers or chemicals. As such, HTM is ideal for long-term monitoring of living organisms in conditions close to their natural settings. We present a case-based review of the principal uses of both techniques and their essential contributions to nanomedicine and nanotoxicology (study of the harmful effects of NMs in living organisms), emphasizing cancer and infectious disease control. The synergic impact of the sequential use of these complementary strategies provides a clear drive for adopting these techniques as interdependent fundamental tools. Graphical abstract

The Turkevich method was optimized to prepare gold nanoparticles (AuNP) stabilized by polyethyleneglycol (PEG) for µCT. Using various independent modalities, we thoroughly characterized the optimized PEG-AuNPs. Here, we show that PEG-AuNPs are retained in the blood and provide a high contrast in the high-resolution µCT imaging of blood vessels and inner organs. The biodistribution is characterized by prolonged circulation in the blood and accumulation in the liver, spleen and skin. The accumulation of AuNP in the skin resulted in the blue discoloration of eyes and the whole skin. In vitro experiments using a leukemic monocyte THP-1 cell line model expressing high levels of NLRP3 demonstrated that the NLRP3inflammasome was not activated by PEG AuNP. Over 9 months, the mice were scanned by µCT and were in good health. Scans in mice using PEG-stabilized AuNPs in this study were sharper, with a higher contrast, when compared to a commercial contrasting agent at the same dose. The PEG-AuNPs were morphologically and chemically stable for at least two years when stored in the refrigerator.

Assessment and prediction for the ecotoxicity of engineered nanoparticles (ENPs) at the community or ecosystem levels represents a critical step toward a comprehensive understanding of the ecological risks of ENPs. Current studies on predicting the ecotoxicity of ENPs primarily focus on the cellular and individual levels, with limited exploration at the community or ecosystem levels. Herein, we present the first of the reports for the direct prediction of aquatic ecological risk for ENPs at the community level using machine learning (ML) approaches in the field of computational toxicology. Specifically, we extensively collected the threshold concentrations of twelve ENPs including metal- and carbon-based nanoparticles for aquatic species, i.e., hazardous concentrations at which 5% of species are harmed (HC5), established by a species sensitivity distribution. Afterwards, we used eight supervised ML methods including Adaboost, artificial neural network, C4.5 decision tree, K-nearest neighbor, logistic regression, Naive Bayes, random forest, and support vector machine to develop nine classification models and four regression models, respectively, for the qualitative and quantitative prediction of HC5. The evaluation of model performance yielded the internal validation accuracy of all classification models ranging from 71.4 to 100%, and the determination coefficient of regression models ranging from 0.702 to 0.999, indicating that the developed models showed good performance. By using a cross-validation method and an application domain characterization, the selected models were further validated to have powerful predictive ability. Furthermore, the incorporation of three nanostructural descriptors (metal oxide sublimation enthalpy, zeta potential, and specific surface area) linked to toxicity mechanisms (the release of metal ions, the stability of dispersions of particles in aqueous suspensions, and the surface properties of the material) effectively enhanced the prediction power and mechanistic interpretability of the selected models. These findings would not only be beneficial in the screening of ENPs with potential high ecological risks that need to be tested as a priority but also contribute to the development of environmental regulations and standards for ENPs. [ABSTRACT FROM AUTHOR]

The formation of a proper fibrin clot is essential during blood coagulation, as abnormal clots can predispose individuals to bleeding or thrombosis. Despite these concerns, there is currently limited understanding of the potential adverse effects of engineered nanomaterials on fibrin clot formation. This is surprising, given that fibrinogen is highly concentrated in plasma and has a large surface area, making it prone to unintended interactions with nanomaterials. In this study, the impact of ultrasmall gold nanoparticles (usGNPs) on fibrin clot formation is investigated. UsGNPs have gained significant interest in biomedical applications due to their unique physicochemical properties and favorable behavior in complex biofluids. It is found that the usGNPs interacted with fibrinogen, delayed the onset of clot formation, and became physically trapped within the forming fibrin matrix. Confocal microscopy showed that the usGNPs disrupted the normal architecture of the fibrin clot, resulting in a less dense network structure. This disruption led to larger clot pore sizes and increased clot permeability to liquid. Considering the potential health risks associated with abnormal clot formation, a detailed examination of the clot formation process should be included in the standard safety assessment of usGNPs and other nanomedicines. [ABSTRACT FROM AUTHOR]

The rapid inclusion of zinc oxide nanoparticles (ZnO NPs) in nanotechnology-based products over the last decade has generated a new threat in the apprehension of the environment. The massive use of zinc nanosized products will certainly be disposed of and be released, eventually entering the aquatic ecosystem, posing severe environmental hazards. Moreover, nanosized ZnO particles owing the larger surface area per volume exhibit different chemical interactions within the aquatic ecosystem. They undergo diverse potential transformations because of their unique physiochemical properties and the feature of receiving medium. Therefore, assessment of their impact is critical not only for scavenging the present situation but also for preventing unintended environmental hazards. Algae being a primary producer of the aquatic ecosystem help assess the risk of massive NPs usage in environmental health. Because of their nutritional needs and position at the base of aquatic food webs, algal indicators exhibit relatively unique information concerning ecosystem conditions. Moreover, algae are presently the most vital part of the circular economy. Hence, it is imperative to understand the physiologic, metabolic, and morphologic changes brought by the ZnO NPs to the algal cells along with the development of the mechanism imparting toxicity mechanism. We also need to develop an appropriate scientific strategy in the innovation process to restrain the exposure of NPs at safer levels. This review provides the details of ZnO NP interaction with algae. Moreover, their impact, mechanism, and factors affecting toxicity to the algae are discussed. [ABSTRACT FROM AUTHOR]

In a changing environmental scenario, acid rain can have a significant impact on aquatic ecosystems. Acidification is known to produce corrosion in metals, hence increasing their harmful effects on the environment, organisms and human health. The prevalent use of metallic nanoparticles (NPs) in everyday products raises concerns regarding exposure and nanotoxicity even in these acidified conditions. We thus report on the cytotoxic and genotoxic potential of nickel oxide (NiO‐NP) and zinc oxide (ZnO‐NP) NPs when suspended in aqueous media in light of pH variations (7.5 and 5). A modified microsuspension method of the Salmonella/microsome assay was adopted, and strains (TA97a, TA98, TA100, TA102) were exposed to NPs (10–1280 μg/plate) with and without a metabolization fraction. The acidic condition favored disaggregation and caused a decrease in NPs size. Mutagenicity was observed in all samples and different strains, with greater DNA base pair substitution damage (TA100 and TA102), but extrinsic conditions (pH) suggest different action mechanisms of NiO‐NP and ZnO‐NP on genetic content. Mutagenic activity was found to increase upon metabolic activation (TA98, TA100, and TA102) demonstrating the bioactivity of NiO‐NP and ZnO‐NP in relation to metabolites generated by the mammalian p450 system in vitro. Modifications in the Salmonella assay methodology increased cell exposure time. The observed responses recommend this modified assay as one of the methodologies of choice for nanoecotoxicological evaluation. These findings emphasize the significance of incorporating the environmental context when evaluating the toxicity of metal‐based NPs. The aim of this study was to explore the role of pH variation in aqueous media on the mutagenic potential of nickel oxide (NiO) and zinc oxide (ZnO) nanoparticles. The acidic condition favored disaggregation and a decrease in the size of the nanoparticles. Mutagenicity was observed for NiO (similar at both pHs) and ZnO (increased at neutral pH). A greater DNA base pair substitution damage was found. Mutagenic responses increase upon metabolic activation (except for TA97a). [ABSTRACT FROM AUTHOR]

Scientists worldwide have noticed that cutting-edge technologies can be used to produce nanoparticles (NPs) in a sustainable and environmentally friendly way, instead of the old methods. However, the effectiveness of this approach for aquatic environments and species still needs to be determined. Therefore, this study aims to compare between the toxicity of green and chemically synthesized copper oxide nanoparticles (GS and CS) CuO NPs at two different concentrations on Nile tilapia (Oreochromis niloticus) using various biomarkers. CuO NPs' formation was proved, and their different characterizations were recorded. Then, the fish samples were randomly allocated in glass aquaria into five groups: one acted as a control group, and the other groups were exposed to two concentrations (25 and 50 mg/L) of GS-CuO NPs and CS-CuO NPs, separately, for 4 days. After the experimental time, in all groups that were exposed to two concentrations of both synthesized CuO NPs, the results revealed that glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and thiobarbituric acid reactive substances (TBARS) levels were elevated in the liver and gills compared to glutathione reduced (GSH) content, which showed a significant decline. Bioaccumulation of Cu was more prevalent in the liver than in the gills, and the highest bioaccumulation capacity was more evident in the groups exposed to CS-CuO NPs. Moreover, the bioaccumulation of Cu caused severe histological changes in the liver and gills. In conclusion, the results suggested that GS-CuO NPs revealed less toxicity than CS-CuO NPs to the examined fish. However, they are still toxic, and their toxic effect cannot be overlooked. [ABSTRACT FROM AUTHOR]

Due to advances in additive manufacturing and prototyping, affordable and rapid microfluidic sensor-integrated assays can be fabricated using additive manufacturing, xurography and electrode shadow masking to create versatile platform technologies aimed toward qualitative assessment of acute cytotoxic or cytolytic events using stand-alone biochip platforms in the context of environmental risk assessment. In the current study, we established a nasal mucosa biosensing platform using RPMI2650 mucosa cells inside a membrane-integrated impedance-sensing biochip using exclusively rapid prototyping technologies. In a final proof-of-concept, we applied this biosensing platform to create human cell models of nasal mucosa for monitoring the acute cytotoxic effect of zinc oxide reference nanoparticles. Our data generated with the biochip platform successfully monitored the acute toxicity and cytolytic activity of 6 mM zinc oxide nanoparticles, which was non-invasively monitored as a negative impedance slope on nasal epithelial models, demonstrating the feasibility of rapid prototyping technologies such as additive manufacturing and xurography for cell-based platform development. [ABSTRACT FROM AUTHOR]

Cosmetic is an enriching source of potentially toxic trace elements due to the use of different chemicals and preservatives during their preparation. The present study presents the structural, morphological, and quantitative analyses of eighteen trace elements in six (n = 6) imported/locally manufactured facial powders using electron microscopy tools (SEM/EDX/TEM), Fourier infrared spectroscopy (FTIR) and inductivity coupled plasma-optical emission spectrophotometry (ICP-OES). SEM/EDX/TEM analyses reveal the sheet-like morphology of the cosmetic products with varying sizes, shapes, and thicknesses. The branded specimens displayed the nano-sized crystalline nanoparticles along with sheets, either deposited on sheets or present in the dispersion. The size of the particles was estimated between 5 and 300 nm. The average contents of the eighteen trace elements determined by ICP-OES are (in µg/g): 7739.43 (Li), 1015.30 (Ca), 514.18 (Fe), 226.61 (Mg), 201.10 (Al), 133.25 (Zn), 83.50 (Na), 11.82 (Mn), 9.05 (K), 1.85 (Ba), 4.96 (Cr), 0.57 (Cu), 0.29 (Pb), 0.10 (Sb), 0.08 (Se), 0.03 (Cd), 0.01 (As) and 0 (Ni). The branded samples showed the lowest fractions, while the locally manufactured specimens exhibited higher contents of potentially toxic trace elements. The metal contents of Li, Ca, Fe, Mg, Al, Zn, and Pb were the highest whereas the K, Mn, and Cr contents were

Background Exposure to nanoparticles (NPs) can occur in a variety of occupational situations. Ultrafine particles of natural and anthropological origin toxicity has been described in epidemiological studies. Meanwhile, the risks associated with NPs exposure are not comprehensively assessed. A wide spectrum of NPs toxicity has been demonstrated, mainly through the induction of oxidative stress and inflammatory mediators. Among the newly described mechanisms of NPs toxicity is the induction of fibrosis via the epithelial-mesenchymal transition (EMT), which is also a key mechanism of cancer metastasis. The effect of NPs on EMT in the context of metastasis has not been sufficiently described so far, and the results of studies do not allow for the formulation of unambiguous conclusions. Therefore, the aim of the work was to determine the biological activity of silver NPs against MDA-MB-436 triple-negative breast cancer cells. Material and Methods Exposure to nanoparticles (NPs) can occur in a variety of occupational situations. Ultrafine particles of natural and anthropological origin toxicity has been described in epidemiological studies. Meanwhile, the risks associated with NPs exposure are not comprehensively assessed. A wide spectrum of NPs toxicity has been demonstrated, mainly through the induction of oxidative stress and inflammatory mediators. Among the newly described mechanisms of NPs toxicity is the induction of fibrosis via the epithelial-mesenchymal transition (EMT), which is also a key mechanism of cancer metastasis. The effect of NPs on EMT in the context of metastasis has not been sufficiently described so far, and the results of studies do not allow for the formulation of unambiguous conclusions. Therefore, the aim of the work was to determine the biological activity of silver NPs against MDA-MB-436 triple-negative breast cancer cells. Results Silver nanoparticles (AgNPs) cause a statistically significant increase in relative expression of all tested mesenchymal EMT markers – cadherin 2, vimentin, matrix metalloproteinase 2 and matrix metalloproteinase 9. At the same time, reduction of epithelial cadherin 1 expression was observed. The level of MDA-MB-436 migration and TGF-beta 1 secretion was slighty increased in AgNPs-treated cells, with no influence on invasion potential. Conclusions Potentially prometastatic effect of AgNPs encourages further work on the safety of nanomaterials. Med Pr Work Health Saf. 2023;74(6):541–8.

Xiaotan Lin,1,2 Tingting Chen1 1School of Basic Medicine, Guangdong Medical University, DongGuan, People’s Republic of China; 2Department of Family Planning, Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, Shenzhen, People’s Republic of ChinaCorrespondence: Tingting Chen, School of Basic Medicine, Guangdong Medical University, DongGuan, People’s Republic of China, Email jkf_ctt@163.comAbstract: Tremendous research efforts have been devoted to nanoparticles for applications in optoelectronics and biomedicine. Over the past decade, quantum dots (QDs) have become one of the fastest growing areas of research in nanotechnology because of outstanding photophysical properties, including narrow and symmetrical emission spectrum, broad fluorescence excitation spectrum, the tenability of the emission wavelength with the particle size and composition, anti-photobleaching ability and stable fluorescence. These characteristics are suitable for optical imaging, drug delivery and other biomedical applications. Research on QDs toxicology has demonstrated QDs affect or damage the biological system to some extent, and this situation is generally caused by the metal ions and some special properties in QDs, which hinders the further application of QDs in the biomedical field. The toxicological mechanism mainly stems from the release of heavy metal ions and generation of reactive oxygen species (ROS). At the same time, the contact reaction with QDs also cause disorders in organelles and changes in gene expression profiles. In this review, we try to present an overview of the toxicity and related toxicity mechanisms of QDs in different target organs. It is believed that the evaluation of toxicity and the synthesis of environmentally friendly QDs are the primary issues to be addressed for future widespread applications. However, considering the many different types and potential modifications, this review on the potential toxicity of QDs is still not clearly elucidated, and further research is needed on this meaningful topic. Keywords: quantum dots, nanotoxicology, nanoparticle, toxicity, cytotoxic

The extensive application of amorphous silica nanoparticles (aSiNPs) in recent years has resulted in unavoidable human exposure in daily life, thus raising widespread concerns regarding the safety of aSiNPs on human health. The particle size is one of the important characteristics of nanomaterials that could influence their toxicity. For the reason that particles with smaller sizes possess larger surface area, which may lead to higher surface activity and biological reactivity. However, due to the complexity of experimental conditions and biological systems, the relationship between the particle size and the toxic effect of aSiNPs remains unclear. Therefore, this systematic review aims to investigate how particle size influences the toxic effect of aSiNPs in vivo and to analyze the relevant experimental factors affecting the size-dependent toxicity of aSiNPs in vivo. We found that 83.8% of 35 papers included in the present review came to the conclusion that smaller-sized aSiNPs exhibited stronger toxicity, though a few papers (6 papers) put forward different opinions. The reasons for smaller aSiNPs manifested greater toxicity were summarized. In addition, certain important experimental factors could influence the size-dependent effects and in vivo toxicity of aSiNPs, such as the synthesis method of aSiNPs, disperse medium of aSiNPs, administration route of aSiNPs, species or strain of experimental animals, sex of experimental animals, aggregation/agglomeration and protein corona of aSiNPs.

The impact of solubility on the toxicity of metal oxide nanoparticles (MONPs) requires further exploration to ascertain the impact of the dissolved and particulate species on response. In this study, FE1 mouse lung epithelial cells were exposed for 2–48 h to 4 MONPs of varying solubility: zinc oxide, nickel oxide, aluminum oxide, and titanium dioxide, in addition to microparticle analogues and metal chloride equivalents. Previously published data from FE1 cells exposed for 2–48 h to copper oxide and copper chloride were examined in the context of exposures in the present study. Viability was assessed using Trypan Blue staining and transcriptomic responses via microarray analysis. Results indicate material solubility is not the sole property governing MONP toxicity. Transcriptional signaling through the 'HIF-1α Signaling' pathway describes the response to hypoxia, which also includes genes associated with processes such as oxidative stress and unfolded protein responses and represents a conserved response across all MONPs tested. The number of differentially expressed genes (DEGs) in this pathway correlated with apical toxicity, and a panel of the top ten ranked DEGs was constructed (Hmox1, Hspa1a, Hspa1b, Mmp10, Adm, Serpine1, Slc2a1, Egln1, Rasd1, Hk2), highlighting mechanistic differences among tested MONPs. The HIF-1α pathway is proposed as a biomarker of MONP exposure and toxicity that can help prioritize MONPs for further evaluation and guide specific testing strategies. [ABSTRACT FROM AUTHOR]