Toxicity Of Nanoparticles Research Articles

The Role of Phthalocyanine-Gold Nanoconjugates (Pc-Au NCs) in Ameliorating the Hepatic and Renal Toxicity-Induced by Silver Nanoparticles (Ag NPs) in Male Rats.

Recently, gold nanoparticles (Au Nps) have gained tremendous attention for its unique properties as a safe nanocarrier for delivering drugs that are used in different disease diagnoses. Although silver nanoparticles (Ag NPs) have been generally applied due to their strong antibacterial, antiviral, antifungal, and antimicrobial properties, their toxicity is a subject of sustained debate, thus requiring further studies. The present study aims to evaluate the potential protective effect of gold nanoparticles and phthalocyanine-gold nanoconjugates (Pc-Au NCs) against the hepatorenal toxicity of silver nanoparticles in male rats. Herein, 60 adult male Rattus norvegicus rats were divided into six equal groups (n = 10/group); the first group was kept as control, the second received gold nanoparticles (Au NPs) intraperitoneally (10 µg/kg) daily for 3 weeks, the third group is gold-phthalocyanine (Pc-Au) group where rats were injected intraperitoneally with gold-phthalocyanine for 3 weeks (10 µg/kg), the fourth group received silver nanoparticles (Ag NPs) (4 mg/kg) daily intraperitoneally for 3 weeks, the fifth group is silver + gold nanoparticles group (Ag + Au), and the sixth is silver + gold-phthalocyanine nanoconjugates (Ag + Pc-Au) group in which rats were intraperitoneally injected firstly with Ag NPs (4 mg/kg) for 3 weeks then with gold or gold-phthalocyanine for another 3 weeks (10 µg/kg). Our results revealed that Ag NPs could increase the serum AST, ALT, ALP, urea, creatinine, and lipid profile and significantly decreased the total protein and albumin. Moreover, histopathological alterations detected in the kidney and the liver of the Ag NPs group included vascular congestion, inflammatory cell infiltration, and tissue distortion. Alongside, exposure to Ag NPs induces hepatic and renal oxidative stress by suppressing the antioxidant-related genes including glutathione peroxidase 1 (gpx1), superoxide dismutase (sod), and catalase (cat). Ag NPs also upregulated the hepatic and renal genes involved in inflammation such as the interleukin-6 (il-6) and tumor necrosis factor-α (tnf-α), nuclear factor kappa B (nf-κβ), apoptosis such as the BCL2 associated X (bax), casp3, and other related to metabolism including asparagine synthetase (asns), suppressor of cytokine signaling 3 (socs3), MYC proto-oncogene (myc), and C-C motif chemokine ligand 2 (ccl2). On the other hand, treatment with Au NPs and Pc-Au NCs could effectively ameliorate the hepatorenal damages induced by Ag NPs and improve liver and kidney architecture and function, especially in the Pc-Au NCs group. Briefly, our study revealed the underlined mechanism of Ag NPs hepatotoxic and nephrotoxic effects and that Pc-Au NCs could alleviate these adverse impacts via their anti-oxidative, anti-apoptotic, and anti-inflammatory activities.

Physiological and transcriptomic responses of silkworms to graphene oxide exposure

The growing use of nanomaterials has sparked significant interest in assessing the insect toxicities of nanoparticles. The silkworm, as an economically important insect, serves as a promising model for studying how insects respond to harmful substances. Here, we conducted a comprehensive investigation on the impact of graphene oxide (GO) on silkworms using a combination of physiological and transcriptome analyses. GO can enter the midguts and posterior silk glands of silkworms. High GO concentrations (> 25 mg/L) significantly (P < 0.01) inhibited larval growth. Additionally, GO (> 5 mg/L) significantly reduced the cocooning rate, and GO (> 15 mg/L) hindered oviduct development and egg laying in silkworms. GO increased the reactive oxygen species content and regulated catalase activity, suggesting that it may affect insect growth by regulating reactive oxygen detoxification. The transcriptome data analysis showed that 35 metabolism-related genes and 20 ribosome biogenesis-related genes were differentially expressed in response to GO, and their expression levels were highly correlated. Finally, we propose that a Ribosome biogenesis–Metabolic signaling network is involved in responses to GO. The research provides a new perspective on the molecular responses of insects to GO.

BIOLOGICAL REACTIONS OF MACROPHAGES TO METAL OXIDE NANOPARTICLES

In our daily lives, nanomaterials are utilized extensively in paints, textiles, food goods, cosmetics, and medicine. Several investigations aim to deter investigations of the physiological effects in various cell types. The innate immune system's macrophages regulate a wide range of biological functions. Depending on the stimulus, macrophages can be activated toward pro- or anti-inflammatory (M1) phenotypes; however, polarization may change in conditions including cancer, autoimmune illnesses, and bacterial and viral infections. Metal oxide nanoparticles have recently gained significant interest due to their diverse range of unique features with applications in research and industry. The production and usage of nanomaterials will rise significantly as the nanotechnology business grows. As a result, testing the consequences of nanomaterial exposure in biological systems is critical. A comparative analysis is conducted on the toxicities of several metal oxide nanoparticles. The significance of biogenically generated metal oxide nanoparticles has been growing in recent years. However, more research is needed to thoroughly characterize the potential toxicity of these nanoparticles to ensure nanosafety and consider environmental views. To that end, nanotoxicology seeks to assess the toxicity of nanomaterials to physicochemical factors such as size and form. In this review, we focus on the biological reactions of macrophages to metal oxide nanoparticles. Because macrophages are the first cells to engage with nanoparticles when they enter the body, they can absorb them through various processes.

Combined toxicity of polyethylene microplastics and nickel oxide nanoparticle on earthworm (Eisenia andrei): oxidative stress responses, bioavailability and joint effect.

The co-occurrence of heavy metals and microplastics (MPs) is an emerging issue that has attracted considerable attention. However, the interaction of nickel oxide nanoparticle (nano-NiO) combined with MPs in soil was poorly researched. Here, experiments were conducted to study the influence of nano-NiO (200mg/kg) and polyethylene (PE) MPs with different concentrations (0.1, 1, and 10%) and sizes (13, 50, and 500µm) on earthworms for 28days. Compared to control, the damage was induced by PE and nano-NiO, which was evaluated by biomarker Integrated Biomarker Response index: version 2 (IBRv2) based on six biomarkers including SOD, POD, CAT, MDA, AChE, Na+/K+-ATPase and cellulase. The majority of the chosen biomarkers showed significant but complicated responses with increasing contaminant concentrations after 28days of exposure. Moreover, the joint effect was assessed as antagonism by the effect addition index (EAI). Overall, this work expands our understanding of the combined toxicity of PE and nano-NiO in soil ecosystems.

Long-Term Accumulation, Biological Effects and Toxicity of BSA-Coated Gold Nanoparticles in the Mouse Liver, Spleen, and Kidneys.

Gold nanoparticles are promising candidates as vehicles for drug delivery systems and could be developed into effective anticancer treatments. However, concerns about their safety need to be identified, addressed, and satisfactorily answered. Although gold nanoparticles are considered biocompatible and nontoxic, most of the toxicology evidence originates from in vitro studies, which may not reflect the responses in complex living organisms. We used an animal model to study the long-term effects of 20 nm spherical AuNPs coated with bovine serum albumin. Mice received a 1 mg/kg single intravenous dose of nanoparticles, and the biodistribution and accumulation, as well as the organ changes caused by the nanoparticles, were characterized in the liver, spleen, and kidneys during 120 days. The amount of nanoparticles in the organs remained high at 120 days compared with day 1, showing a 39% reduction in the liver, a 53% increase in the spleen, and a 150% increase in the kidneys. The biological effects of chronic nanoparticle exposure were associated with early inflammatory and fibrotic responses in the organs and were more pronounced in the kidneys, despite a negligible amount of nanoparticles found in renal tissues. Our data suggest, that although AuNPs belong to the safest nanomaterial platforms nowadays, due to their slow tissue elimination leading to long-term accumulation in the biological systems, they may induce toxic responses in the vital organs, and so understanding of their long-term biological impact is important to consider their potential therapeutic applications.

Zinc oxide nanoparticles mediate bacterial toxicity in Mueller-Hinton Broth via Zn2.

As antibiotic resistance increases and antibiotic development dwindles, new antimicrobial agents are needed. Recent advances in nanoscale engineering have increased interest in metal oxide nanoparticles, particularly zinc oxide nanoparticles, as antimicrobial agents. Zinc oxide nanoparticles are promising due to their broad-spectrum antibacterial activity and low production cost. Despite many studies demonstrating the effectiveness of zinc oxide nanoparticles, the antibacterial mechanism is still unknown. Previous work has implicated the role of reactive oxygen species such as hydrogen peroxide, physical damage of the cell envelope, and/or release of toxic Zn2+ ions as possible mechanisms of action. To evaluate the role of these proposed methods, we assessed the susceptibility of S. aureus mutant strains, ΔkatA and ΔmprF, to zinc oxide nanoparticles of approximately 50 nm in size. These assays demonstrated that hydrogen peroxide and electrostatic interactions are not crucial for mediating zinc oxide nanoparticle toxicity. Instead, we found that Zn2+ accumulates in Mueller-Hinton Broth over time and that removal of Zn2+ through chelation reverses this toxicity. Furthermore, we found that the physical separation of zinc oxide nanoparticles and bacterial cells using a semi-permeable membrane still allows for growth inhibition. We concluded that soluble Zn2+ is the primary mechanism by which zinc oxide nanoparticles mediate toxicity in Mueller-Hinton Broth. Future work investigating how factors such as particle morphology (e.g., size, polarity, surface defects) and media contribute to Zn2+ dissolution could allow for the synthesis of zinc oxide nanoparticles that possess chemical and morphological properties best suited for antibacterial efficacy.

Ferroptosis is involved in trophoblast cells cytotoxicity induced by black phosphorus nanoparticles

Black phosphorus (BP) is a new type of nanomaterial, which has been widely used in many biomedical fields due to its superior properties, but there are few studies on the toxicity of BP, especially in the reproductive system. To explore the effects of BP exposure on reproduction and reveal its molecular mechanism, we firstly investigated the potential toxicity of black phosphorus nanoparticles (BPNPs) in vivo. The results showed that BP exposure in pregnant mice can reduce the weight of fetal mice and placenta. H&E staining further indicated the changes of placental cross-section and vascular remodeling after BP treatment. Then, human exvillous trophoblast HTR8/SVneo was treated with different concentrations of BPNPs. We found that BPNPs induced significant cytotoxicity, including dose-dependent reduction of cell viability and proliferation. Trophoblast cell migration and invasion were also impaired by BPNPs exposure. Moreover, pretreatment with Cytochalasin D (Cyto-D), a classical phagocytic inhibitor, alleviated the decline of cell viability induced by BPNPs. Transcriptome sequencing showed that BPNPs exposure led to ferroptosis. Subsequently, the related indexes of ferroptosis were detected, including increase of iron ion concentration, decrease of the ferroptosis marker, GPX4 (Glutathione Peroxidase 4), increase of FTL (Ferritin Light Chain), and increase of lipid peroxidation indexes (MDA level and decrease of GSH level). In addition, ferroptosis inhibitors (Fer-1 and DFO) pretreatment can alleviate both the cytotoxic effects and functional impairment induced by BPNPs. In summary, our study confirmed the reproductive toxicity of BPNPs for the first time, and constructed BPNPs injury model in vitro using human villus trophoblast cells and revealed the role of ferroptosis in this process, which deepened our understanding of the biosafety of black phosphorus nanomaterials.

Development and Characterization of Gold Nanoparticles Conjugates to Increase Bioavailability of 6-Gingerol

6-Gingerol, an abundant component of Zingiber officinale, acts as a cardiotonic and is also used in the treatment of cancer disease, but its low solubility makes it very challenging in therapeutic applications. As we are all aware of the metal toxicity of nanoparticles, here we are using gold metal because gold nanoparticles are found to have lower toxicity than other metals. In this study, we prepared optimized conjugated gold nanoparticles of 6-Gingerol (Au-6G-PVP-NPs) by chemical reduction method using polyvinylpyrrolidone, a biocompatible and biodegradable polymer, to increase the bioavailability and solubility of 6-Gingerol. The prepared nanoparticle conjugate was evaluated on different parameters such as pH, solubility, Zeta potential, TEM, DLS, polydispersity index, in vitro release, and stability studies to meet the criteria. The study concluded that gold nanoparticles conjugated with 6-Gingerol showed good solubility in gastric pH, effective drug release, and were more stable than free 6-Gingerol. Hence, it can be concluded that these conjugates can be used for cardiac disease as well as cancer treatment due to their good bioavailability, drug release, improved biocompatibility, stability, and decreased cytotoxicity.

A Role of Biosynthesized Zinc Oxide Nanoparticles (ZnO NPs) for Enhancing Seed Quality: A Review

Abiotic and biotic stresses impact seed growth, resulting in economic losses. Seeds are being subjected to an increasing number of biotic and abiotic stress combinations as a result of global warming and climate change, which has adverse effects on their growth and production. Drought, flood, salinity, heavy mineral contamination, cold, and heat were all found to have a negative impact on seed germination. Because of their massive surface area-to-volume ratio, nanoparticles—microscopic pieces with a nanoscale dimension ranging from 1-100 nm—have exceptional thermal conductivity, catalytic reactivity, nonlinear optical performance, and chemical durability. There are various methods for creating nanoparticles, such as chemical, physical, and biological ones. However, because dangerous chemical compounds are used as reducing agents, the chemical and physical procedures are expensive, complicated, and might be hazardous to the environment. The synthesis of nanoparticles using green approaches may be easily scaled up, and they are also cost-effective. Because of their superior qualities, greenly coordinated nanoparticles are currently preferred over traditionally delivered NPs. Green synthesis approaches are particularly appealing due to their ability to reduce nanoparticle toxicity. The use of vitamins, amino acids, and plant extracts has increased as a result. While dangerous and extremely hazardous substances are used in the chemical and physical processes that may cause environmental issues, capping and reducing agents are essential to the synthesis of nanoparticles. The capping or reducing agent used in physical and chemical processes is expensive. When used as a seed treatment, nanoparticles can enhance germination as well as the length, vigor, viability, and quality of the seedlings. This paper aims to provide an overview and evaluation of zinc oxide nanoparticles (ZnO NPs) as a potential substitute for biosynthesised nanoparticles in seed quality improvement.

Exploring the Effects of Graphene-Based Nanoparticles on Early Salmonids Cardiorespiratory Responses, Swimming and Nesting Behavior.

Graphene-based nanomaterials are exceptionally attractive for a wide range of applications, raising the likelihood of the release of graphene-containing nanoparticles into aquatic environments. The growing use of these carbon nanomaterials in different industries highlights the crucial need to investigate their environmental impact and evaluate potential risks to living organisms. The current investigation evaluated the nanotoxicity of graphene (nanoflakes) and graphene oxide (GO) nanoparticles on the cardiorespiratory responses (heart rate, gill ventilation frequency), as well as the swimming and nesting behavioral parameters of early stage larvae and juvenile salmonids. Both short-term (96 h) and long-term (23 days) exposure experiments were conducted using two common species: brown trout (Salmo trutta) and rainbow trout (Oncorhynchus mykiss). The findings demonstrated notable alterations in fish nesting behavior, swimming performance, and cardiorespiratory functions, indicating the potential toxicity of nanoparticles. This impact was observed at both physiological and whole-organismal levels in salmonids at early stages. Future investigations should explore different types of nanocarbons and their potential enduring effects on fish population structure, considering not only individual survival but also broader aspects of development, including feeding, reproductive, and other social dynamics.

Exploring the antibiofilm and toxicity of tin oxide nanoparticles: Insights from in vitro and in vivo investigations

Background informationThe advancement of biological-mediated nanoscience towards higher levels and novel benchmarks is readily apparent, owing to the use of non-toxic synthesis processes and the incorporation of various additional benefits. This study aimed to synthesize stable tin oxide nanoparticles (SnO2-NPs) using S. rhizophila as a mediator. MethodsThe nanoparticles that were created by biosynthesis was examined using several analytical techniques, including Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM), X-ray diffraction (XRD), UV–visible (UV–vis) spectroscopy, and energy dispersive X-ray spectroscopy (EDS). ResultsThe results obtained from the characterization techniques suggest that S. rhizophila effectively catalyzed the reduction of SnCl2 to SnO2-NPs duration of 90 min at ambient temperature with the ƛmax of 328 nm. The size of the nano crystallite formations was measured to be 23 nm. The present study investigates nanoscale applications' antibacterial efficacy against four bacterial strains, including Klebsiella Sp, Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. The observed zone of inhibition for the nanoparticles (NPs) varied from 10 to 25 mm. The research findings demonstrate that the nanoparticles (NPs) are effective as antibacterial, phytotoxic, and cytotoxic agents.

Nanotechnology and malaria: Evaluation of efficacy and toxicity of green nanoparticles.

Malaria is a global health problem that causes 1.5-2.7 million deaths worldwide each year. Resistance to antimalarial drugs in malaria parasites and to insecticides in vectors is one of the most serious issues in the fight against the disease. Moreover, the lack of an effective vaccine against malaria is still a major concern. Recent developments in nanotechnology have resulted in new prospects for the fight against malaria, especially by obtaining metal nanoparticles (NPs) that are less toxic, highly biocompatible, environmentally friendly, and less expensive. Numerous studies have been conducted on the synthesis of green NPs using plants and microorganisms (bacteria, fungi, algae, actinomycetes, and viruses). To our knowledge, there is no literature review that compares toxicities and antimalarial effects of some existing metallic nanoparticles revealing their advantages and disadvantages. The purpose of this review is to assess the metal NPs obtained through various green synthesis processes, to display the worth of future malaria research, and to determine future strategies. The literature review revealed that there are very limited studies on green NPs covering all stages of malaria parasites. Additionally, green metal nanoparticles have yet to be studied for their possible toxic effects on infected as well as healthy erythrocytes. Moreover, the toxicities of green metal NPs obtained from various sources differed according to concentration, size, shape, synthesis method, and surface charge, indicating the necessity of optimizing the methods used in future studies. This work has investigated the effectiveness of green metal nanoparticles synthesized from different sources against malaria, as well as their advantages and disadvantages. It was concluded that studies on the toxic properties of green nanoparticles would be very important for future stages.

Unveiling the molecular networks underlying cellular impairment in Saccharomyces cerevisiae: investigating the effects of magnesium oxide nanoparticles on cell wall integrity and endoplasmic reticulum stress response.

Nanoparticles, particularly magnesium oxide nanoparticles (MgO-NPs), are increasingly utilized in various fields, yet their potential impact on cellular systems remains a topic of concern. This study aimed to comprehensively investigate the molecular mechanisms underlying MgO-NP-induced cellular impairment in Saccharomyces cerevisiae, with a focus on cell wall integrity, endoplasmic reticulum (ER) stress response, mitochondrial function, lipid metabolism, autophagy, and epigenetic alterations. MgO-NPs were synthesized through a chemical reduction method, characterized for morphology, size distribution, and elemental composition. Concentration-dependent toxicity assays were conducted to evaluate the inhibitory effect on yeast growth, accompanied by propidium iodide (PI) staining to assess membrane damage. Intracellular reactive oxygen species (ROS) accumulation was measured, and chitin synthesis, indicative of cell wall perturbation, was examined along with the expression of chitin synthesis genes. Mitochondrial function was assessed through Psd1 localization, and ER structure was analyzed using dsRed-HDEL marker. The unfolded protein response (UPR) pathway activation was monitored, and lipid droplet formation and autophagy induction were investigated. Results demonstrated a dose-dependent inhibition of yeast growth by MgO-NPs, with concomitant membrane damage and ROS accumulation. Cell wall perturbation was evidenced by increased chitin synthesis and upregulation of chitin synthesis genes. MgO-NPs impaired mitochondrial function, disrupted ER structure, and activated the UPR pathway. Lipid droplet formation and autophagy were induced, indicating cellular stress responses. Additionally, MgO-NPs exhibited differential cytotoxicity on histone mutant strains, implicating specific histone residues in cellular response to nanoparticle stress. Immunoblotting revealed alterations in histone posttranslational modifications, particularly enhanced methylation of H3K4me. This study provides comprehensive insights into the multifaceted effects of MgO-NPs on S. cerevisiae, elucidating key molecular pathways involved in nanoparticle-induced cellular impairment. Understanding these mechanisms is crucial for assessing nanoparticle toxicity and developing strategies for safer nanoparticle applications.

Metal nanoparticle-induced effects on green toads (Amphibia, Anura) under climate change: conservation implications.

The toxicity of aluminum oxide (Al2O3), copper oxide (CuO), iron oxide (Fe3O4), nickel oxide (NiO), zinc oxide (ZnO), and titanium dioxide (TiO2) nanoparticles (NPs) on amphibians and their interaction with high temperatures, remain unknown. In this study, we investigated the survival, developmental, behavioral, and histological reactions of Bufotes viridis embryos and larvae exposed to different NPs for a duration of 10 days, using lethal concentrations (LC25%, LC50%, and LC75% mg/L) under both ambient (AT: 18 °C) and high (HT: 21 °C) temperatures. Based on LC, NiONPs > ZnONPs > CuONPs > Al2O3NPs > TiO2NPs > Fe3O4NPs showed the highest mortality at AT. A similar pattern was observed at HT, although mortality occurred at lower concentrations and Fe3O4NPs were more toxic than TiO2NPs. The results indicated that increasing concentrations of NPs significantly reduced hatching rates, except for TiO2NPs. Survival rates decreased, abnormality rates increased, and developmental processes slowed down, particularly for NiONPs and ZnONPs, under HT conditions. However, exposure to low concentrations of Fe3O4NPs for up to 7 days, CuONPs for up to 72 h, and NiO, ZnONPs, and TiO2NPs for up to 96 h did not have a negative impact on survival compared with the control group under AT. In behavioral tests with larvae, NPs generally induced hypoactivity at AT and hyperactivity at HT. Histological findings revealed liver and internal gill tissue lesions, and an increase in the number of melanomacrophage centers at HT. These results suggest that global warming may exacerbate the toxicity of metal oxide NPs to amphibians, emphasizing the need for further research and conservation efforts in this context.

Remediation of Metal Oxide Nanotoxicity with a Functional Amyloid.

Understanding the environmental health and safety of nanomaterials (NanoEHS) is essential for the sustained development of nanotechnology. Although extensive research over the past two decades has elucidated the phenomena, mechanisms, and implications of nanomaterials in cellular and organismal models, the active remediation of the adverse biological and environmental effects of nanomaterials remains largely unexplored. Inspired by recent developments in functional amyloids for biomedical and environmental engineering, this work shows their new utility as metallothionein mimics in the strategically important area of NanoEHS. Specifically, metal ions released from CuO and ZnO nanoparticles are sequestered through cysteine coordination and electrostatic interactions with beta-lactoglobulin (bLg) amyloid, as revealed by inductively coupled plasma mass spectrometry and molecular dynamics simulations. The toxicity of the metal oxide nanoparticles is subsequently mitigated by functional amyloids, as validated by cell viability and apoptosis assays in vitro and murine survival and biomarker assays in vivo. As bLg amyloid fibrils can be readily produced from whey in large quantities at a low cost, the study offers a crucial strategy for remediating the biological and environmental footprints of transition metal oxide nanomaterials.

Interaction of water salinity and titanium dioxide nanoparticle (TiO2) exposure in the Pacific oyster, Crassostrea gigas: immune and antioxidant system responses

Titanium dioxide nanoparticles (TiO2) are released into the natural waters in different ways and cause toxicity to aquatic life. Although various studies have reported the toxicity of nanoparticles for aquatic animals, there is limited information regarding the effects of environmental factors, especially salinity, on their toxicity. Simultaneous effects of TiNPs and water salinity were studied in the Pacific oyster, Crassostrea gigas. Oysters were exposed to sub-lethal concentrations of TiNPs (low concentration: 50 µg/l, middle concentration: 500 µg/l, high concentration: 5000 µg/l) at different water salinities (Extremely low salinity: 5 g/l, low salinity: 15 g/l, middle salinity: 25 g/l, high salinity (normal salinity): 35 g/l) for 96 h. After nano-TiO2 exposure, the immune components in hemolymph (total hemocyte concentration [THC], phagocytosis), antioxidant enzyme activities in digestive gland (superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase), oxidation stress index (malondialdehyde) in gills and the expression of immune-related genes (Vav-3 protein, cofilin, Galectin 4, pro-Cathepsin L, Rho protein, Ficolin, LPS/-1,3-glucan protein, Lysozyme, Defensin) in hemocytes were measured. The THC, phagocytosis, antioxidant enzyme activities, and immune-related gene expressions mostly decreased at salinities of 5 and 15 g/l in response to 500–5000 µg/l nano-TiO2 compared to non-exposed oysters and 50 µg/l nano-TiO2 group. An increase in water salinity up to 35 g/l mitigated the depressing effects of the nano-TiO2 on the immune and antioxidant components of the oysters. Exposure of oysters to 500–5000 µg/l nano-TiO2-induced oxidative stress at salinities of 5 and 15, since malondialdehyde levels were higher in these treatments compared to control and those in 50 µg/l nano-TiO2 group. The increase of salinity up to 35 g/l ameliorated the TiO2-induced oxidative stress. The results of the present study showed that the toxic impacts of nano-TiO2 can be ameliorated in the Pacific oyster with increase in water salinity, as the immune components, antioxidant enzyme activities recovered and oxidative stress mitigated when the salinity increased up to 35 g/l.

Integrative transcriptomic and metabolomic analyses reveals the toxicity and mechanistic insights of bioformulated chitosan nanoparticles against Magnaporthe oryzae

Rice blast, an extremely destructive disease caused by the filamentous fungal pathogen Magnaporthe oryzae, poses a global threat to the production of rice (Oryza sativa L.). The emerging trend of reducing dependence on chemical fungicides for crop protection has increased interest in exploring bioformulated nanomaterials as a sustainable alternative antimicrobial strategy for effectively managing plant diseases. Herein, we used physiomorphological, transcriptomic, and metabolomic methods to investigate the toxicity and molecular action mechanisms of moringa–chitosan nanoparticles (M–CNPs) against M. oryzae. Our results demonstrate that M–CNPs exhibit direct antifungal properties by impeding the growth and conidia formation of M. oryzae in a concentration-dependent manner. Propidium iodide staining indicated concentration-dependent significant apoptosis (91.33%) in the fungus. Ultrastructural observations revealed complete structural damage in fungal cells treated with 200 mg/L M–CNPs, including disruption of the cell wall and destruction of internal organelles. Transcriptomic and metabolomic analyses revealed the intricate mechanism underlying the toxicity of M–CNPs against M. oryzae. The transcriptomics data indicated that exposure to M–CNPs disrupted various processes integral to cell membrane biosynthesis, aflatoxin biosynthesis, transcriptional regulation, and nuclear integrity in M. oryzae., emphasizing the interaction between M–CNPs and fungal cells. Similarly, metabolomic profiling demonstrated that exposure to M–CNPs significantly altered the levels of several key metabolites involved in the integral components of metabolic pathways, microbial metabolism, histidine metabolism, citrate cycle, and lipid and protein metabolism in M. oryzae. Overall, these findings demonstrated the potent antifungal action of M–CNPs, with a remarkable impact at the physiological and molecular level, culminating in substantial apoptotic-like fungal cell death. This research provides a novel perspective on investigating bioformulated nanomaterials as antifungal agents for plant disease control.

The addition of mammalian cell culture medium impacts nanoparticle toxicity in zebrafish

Engineered nanomaterials (ENMs) are ubiquitous in contemporary applications, yet their environmental and human health impacts remain inadequately understood. This study addresses the challenge of identifying potential risks associated with ENM exposure by highlighting the significant variability in existing research methodologies. Without a systematic collection of toxicological data that encompasses standardized materials, relevant platforms, and assays, the task of identifying potential risks linked to ENM exposure becomes an intricate challenge. In vitro assessments often use media rich in ionic species, such as RPMI and fetal bovine serum (FBS). Zebrafish embryos, known to develop normally in low-ionic environments, were exposed to Cerium Oxide, Zinc Oxide, and Graphene Oxides in different media at varying concentrations. Here, we discovered that zebrafish embryos tolerated a mix of 80 % RPMI, 2 % FBS, and 1 % antibiotic cocktail. The results revealed that adverse effects observed in zebrafish with certain nanomaterials in Ultra-Pure (UP) water were mitigated in cell culture medium, emphasizing the importance of revisiting previously considered non-toxic materials in vitro. The zebrafish results underscore the importance of utilizing a multidimensional in vivo platform to gauge the biological activity of nanomaterials accurately.

In silico assessment of nanoparticle toxicity powered by the Enalos Cloud Platform: Integrating automated machine learning and synthetic data for enhanced nanosafety evaluation

The rapid advance of nanotechnology has led to the development and widespread application of nanomaterials, raising concerns regarding their potential adverse effects on human health and the environment. Traditional (experimental) methods for assessing the nanoparticles (NPs) safety are time-consuming, expensive, and resource-intensive, and raise ethical concerns due to their reliance on animals. To address these challenges, we propose an in silico workflow that serves as an alternative or complementary approach to conventional hazard and risk assessment strategies, which incorporates state-of-the-art computational methodologies. In this study we present an automated machine learning (autoML) scheme that employs dose-response toxicity data for silver (Ag), titanium dioxide (TiO2), and copper oxide (CuO) NPs. This model is further enriched with atomistic descriptors to capture the NPs’ underlying structural properties. To overcome the issue of limited data availability, synthetic data generation techniques are used. These techniques help in broadening the dataset, thus improving the representation of different NP classes. A key aspect of this approach is a novel three-step applicability domain method (which includes the development of a local similarity approach) that enhances user confidence in the results by evaluating the prediction’s reliability. We anticipate that this approach will significantly expedite the nanosafety assessment process enabling regulation to keep pace with innovation, and will provide valuable insights for the design and development of safe and sustainable NPs. The ML model developed in this study is made available to the scientific community as an easy-to-use web-service through the Enalos Cloud Platform (www.enaloscloud.novamechanics.com/sabydoma/safenanoscope/), facilitating broader access and collaborative advancements in nanosafety.

Abstract 6739: Efficacy and toxicity of microbial mimetic mesoporous silica nanoparticles in a mouse model of ovarian cancer

Abstract Ovarian cancer is predominately left undetected and untreated until the later stages of the disease where it becomes incredibly difficult to treat. Preclinical studies demonstrate that immunotherapy can be highly effective. Our lab has been working on an immunotherapy approach to treat women with ovarian cancer that utilizes mesoporous silica nanoparticles(MSN). MSN that present pathogen-associated molecular patterns (PAMPS) are able to significantly reduce tumor burden in mouse models of serous epithelial ovarian cancer when administered by intraperitoneal injection. These microbial mimetic particles are decorated with polyethyleneimine (PEI), CpG oligonucleotide, and monophosphoryl lipid A (MPLA). When in the presence of antigen presenting cells, they bind to Toll-like receptors (TLR) present on the cell surface and within the endosome. To better understand mechanisms underlying their efficacy, we injected fluorescent MSN-PEI-CpG-MPLA (100 or 500 nm) or unmodified MSN into mice with advanced ovarian cancer. The particles, regardless of the presence of TLR-agonists, were rapidly internalized by myeloid cells, with trafficking almost exclusively to immune clusters located in tumor-burdened adipose tissues when administered by intraperitoneal injection. Conversely, intravenous injection of MSN-PEI-CpG-MPLA led to predominate accumulation in liver, with no particles found in tertiary lymphoid clusters 24 hours post injection. Furthermore, unlike intraperitoneal injection, intravenous injection of MSN-PEI-CpG-MPLA was without therapeutic effect. Currently we are studying MSN safety and the impact of administration route and dose on efficacy and cytotoxicity. In summary, MSN, with and without TLR agonists, are trafficked by myeloid cells to tumor-burdened fat-associated lymphoid clusters when administered by intraperitoneal injection. Intraperitoneal injection of TLR-agonist modified MSN effectively reduces tumor burden in mice with ovarian cancer. Citation Format: Lorel Y. Medina, Rita E. Serda, Benjamin Marwedel, Melanie S. Jun, Josh Adogola. Efficacy and toxicity of microbial mimetic mesoporous silica nanoparticles in a mouse model of ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6739.