An insight into impact of nanomaterials toxicity on human health.

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.

Drosophila melanogaster as a tractable eco-environmental model to unravel the toxicity of micro- and nanoplastics.

Micro- and nanoplastics have emerged as pervasive environmental pollutants with potential ecotoxicological impacts on various organisms, including the model organismDrosophila melanogaster. Here we comprehensively synthesize current research on the adverse effects of micro- and nanoplastics onDrosophila, 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 inDrosophila. 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 onDrosophiladepend 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.

Synergistic anticancer effects and reduced genotoxicity of silver nanoparticles and tamoxifen in breast cancer cells.

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.

Biodistribution and toxic potential of silver nanoparticles when introduced to the female rat reproductive tract.

The prevalence of ionic silver and silver nanomaterials in hygiene products has been increasing due to their antimicrobial activity. While numerous studies have examined the effects of nanosilver in laboratory settings, there is a limited understanding of its impact on reproductive tissues, as well as its biodistribution and toxicity upon intra-vaginal exposure. If ionic or nanosilver enters adjacent and internal tissues via intra-vaginal exposure, the overuse of hygiene products containing silver may potentially threaten woman's health. This study investigated the effects of intra-vaginal silver exposure in Female Fischer 344 rats to single and multiple doses of a commercial product containing silver, along with standard nanosilver materials. Custom tampons were developed to simulate practical usage scenarios. The analysis of tissue biodistribution revealed that epithelial penetration and redistribution of silver was observed with most administered silver eliminated in feces (8-44 %), and secondary tissues containing 1-18 % of the dose, predominantly localized in the reproductive tract. In a subsequent toxicity study, vaginal histopathology indicated a cellular inflammatory reaction (neutrophil infiltration) associated with the presence of foreign silver material upon a single administration. Interestingly, no noticeable difference in histopathology incidence was observed upon multiple exposures to silver compared to the control group. Clinical chemistry and hematology analyses following acute exposure to silver nanomaterials showed no significant abnormalities. Overall, acute vaginal exposure to silver nanomaterials and ionic silver resulted in limited silver persistence, local tissue reactivity, epithelial penetration of silver resulting in accumulation in distant organs, and elimination primarily through feces. In vitro data suggested potential alterations in normal vaginal flora. Long-term studies are still lacking in this area.

Comparative study of influence of Cu, CuO nanoparticles and Cu2+ on rainbow trout (Oncorhynchus mykiss W.) spermatozoa.

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.

Cellular uptake of multi-walled carbon nanotubes is associated to genotoxic and teratogenic effects towards the freshwater diatom Nitzschia linearis.

The increase in industrial production of multi-walled carbon nanotubes (MWCNTs) raises concerns about their potential adverse effects associated to environmental releases, especially in aquatic environments where they are likely to accumulate. This study focuses on the environmental impact of MWCNTs, specifically on a benthic freshwater diatom (Nitzschia linearis), which plays a major role in the primary production of water bodies. The obtained results indicate that exposure to MWCNTs in the presence of natural organic matter (NOM) inhibits diatom's growth in a dose-dependent manner after 72 h of exposure. Interestingly, the photosystem II quantum yield (PSIIQY) in diatoms remains unaffected even after exposure to MWCNTs at 10 mg/L. After 48 h of exposure, MWCNTs are found to bind preferentially to extracellular polymeric substances (EPS) produced by diatoms, which could decrease their toxicity by limiting their interaction with this organism. However, measurement of genotoxicity and teratogenicity in diatoms exposed to MWCNTs revealed that the exposure to MWCNTs increased the occurrence of cells with micronuclei and abnormal frustules. Microscopy analyses including two-photon excitation microscopy (TPEM) revealed the internalization of MWCNTs. Investigations of the diatom's frustule structure using Scanning electron microscopy (SEM) indicated that the presence of pore structures constitutes a pathway allowing MWCNTs uptake. The presence in the diatom's cytoplasm of MWCNTs might possibly induce disturbances of the cellular components, leading to the observed genotoxic and teratogenic effects. In view of previous studies, this work underscores the need for further studies on the interaction between nanomaterials and different diatom species, given the species-specific nature of the interactions.

Diazepam nanocapsules as an alternative for sleep induction: Development study and toxicity assessment.

Diazepam (DZP) is a sedative medication prescribed to treat anxiety and as a sleep inducer, although its residual effects are unfavorable to patients. Nanotechnology represents a tool to improve the pharmacological characteristics of drugs, reducing their side effects. This study aimed to develop and characterize DZP nanocapsules and to evaluate their toxicity in alternative models and the hypnotic-sedative effect in mice. Nanocapsules were prepared by the nanoprecipitation method and properly characterized. Long-term and accelerated stability studies were performed. The in vitro release profile was determined by diffusion in Franz cells. The safety of the formulation was evaluated in the Caenorhabditis elegans (C. elegans) and the oral acute toxicity in mice. Pharmacological evaluation was performed using thiopental-induced sleeping time. DZP was successfully incorporated into Poly-(ɛ-caprolactone) (PCL) nanocapsules, with high entrapment efficiency. The nanocapsule did not affect the development or survival of C. elegans, different from the free drug, which affected the nematode development at the higher tested dose. No signs of toxicity, nor body mass or feed consumption changes were observed during the 14 days evaluated. Finally, this innovative formulation carrying DZP can produce a hypnotic-effect at a reduced dose compared to the free drug, with no toxicity in alternative models.

Effects of metal oxide nanoparticles on healthy and psoriasis-like human epidermal keratinocytes in vitro.

The use of metal oxide nanoparticles (NPs) in skincare products has significantly increased human skin exposure, raising safety concerns. Whilst NP's ability to penetrate healthy skin is minimal, studies have demonstrated that metal oxide NPs can induce toxicity in keratinocytes through direct contact. Moreover, NP's effect on common skin disorders like psoriasis, where barrier impairments and underlying inflammation could potentially increase NP penetration and worsen nanotoxicity is largely unstudied. In this paper, we investigated whether psoriasis-like human keratinocytes (Pso HKs) would exhibit heightened toxic responses to titanium dioxide (TiO2), zinc oxide (ZnO), and/or silica (SiO2) NPs compared to healthy HKs. Cells were exposed to each NP at concentrations ranging between 0.5 and 500 µg/ml for 6, 24, and 48 h. Amongst the metal oxide NPs, ZnO NPs produced the most pronounced toxic effects in both cell types, affecting cell viability, inducing oxidative stress, and activating the inflammasome pathway. Notably, only in ZnO NPs-treated Pso HKs, trappin-2/pre-elafin was cleaved intracellularly through a non-canonical process. In addition, tissue remodelling-related cytokines were upregulated in ZnO NP-treated Pso HKs. The full impact of the observed outcomes on psoriatic symptoms will need further evaluation. Nonetheless, our findings indicate the importance of understanding the sub-lethal impacts of NP exposures on keratinocytes, even though direct exposure may be low, particularly in the context of skin disorders where repeated and long-term exposures are anticipated.

Zinc oxide nanoparticles disrupt the mammary epithelial barrier via Z-DNA binding protein 1-triggered PANoptosis.

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.

Analysis of Biodistribution and in vivo Toxicity of Varying Sized Polystyrene Micro and Nanoplastics in Mice.

Introduction: Studies have shown that microplastics (MPs) and nanoplastics (NPs) could accumulate in the human body and pose a potential threat to human health. The purpose of this study is to evaluate the biodistribution and toxicity of MPs/NPs with different particle sizes comprehensively and thoroughly. Methods: The purpose of this study was to investigate the biodistribution and in vivo toxicity of polystyrene (PS) MPs/NPs with different sizes (50 nm, 100 nm, and 500 nm). The BALB/c mice were given 100 µL of PS50, PS100 and PS500 at the dosage of 1 mg/kg BW or 10 mg/kg BW, respectively, by gavage once a day. After 28 consecutive days of treatment, the biodistribution of differently sized PS MPs/NPs was determined through cryosection fluorescence microscopy and fluorescent microplate reader analysis, and the subsequent effects of differently sized PS MPs/NPs on histopathology, hematology and blood biochemistry were also evaluated. Results: The results showed that the three different sizes of PS MPs/NPs were distributed in the organs of mice, mainly in the liver, spleen, and intestine. At the same time, the smaller the particle size, the more they accumulate in the body and more easily penetrate the tissue. During the whole observation period, no abnormal behavior and weight change were observed. The results of H&E staining showed that no severe histopathological abnormalities were observed in the main organs in the low-dose exposure group, while. Exposure of three sizes of PS MPs/NPs could cause some changes in hematological parameters or biochemical parameters related to heart, liver, and kidney function; meanwhile, there were size- and dose-dependencies. Conclusion: The biological distribution and toxicity of plastic particles in mice were more obvious with the decrease of particle size and the increase of concentration of plastic particles. Compared with MPs, NPs were easier to enter the tissues and produce changes in liver, kidney, and heart functions. Therefore, more attention should be paid to the toxicity of NPs.

Molecular characterization and transcriptional response of Lactuca sativa seedlings to co-exposure to graphene nanoplatelets and titanium dioxide nanoparticles.

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.

Silver nanoparticles induce formation of multi-protein aggregates that contain cadherin but do not colocalize with nanoparticles.

Silver nanoparticles (AgNPs) are increasingly incorporated in diverse products to confer antimicrobial properties. They are released into the environment during manufacture, after disposal, and from the products during use. Because AgNPs bioaccumulate in brain, it is important to understand how they interact with neural cell physiology. We found that the focal adhesion (FA)-associated protein cadherin aggregated in a dose-dependent response to AgNP exposure in differentiating cultured B35 neuroblastoma cells. These aggregates tended to colocalize with F-actin inclusions that form in response to AgNP and also contain ß-catenin. However, using hyperspectral microscopy, we demonstrate that these multi-protein aggregates did not colocalize with the AgNPs themselves. Furthermore, expression and organization of the FA protein vinculin did not change in cells exposed to AgNP. Our findings suggest that AgNPs activate an intermediate mechanism which leads to formation of aggregates via specific protein-protein interactions. Finally, we detail the changes in hyperspectral profiles of AgNPs during different stages of cell culture and immunocytochemistry processing. AgNPs in citrate-stabilized solution present mostly blue with some rainbow spectra and these are maintained upon mounting in Prolong Gold. Exposure to tissue culture medium results in a uniform green spectral shift that is not further altered by fixation and protein block steps of immunocytochemistry.

Implications of environmental nanoparticles on neurodegeneration.

The ubiquity of nanoparticles, sourced from both natural environments and human activities, presents critical challenges for public health. While offering significant potential for innovative biomedical applications-especially in enhancing drug transport across the blood-brain barrier-these particles also introduce possible hazards due to inadvertent exposure. This concise review explores the paradoxical nature of nanoparticles, emphasizing their promising applications in healthcare juxtaposed with their potential neurotoxic consequences. Through a detailed examination, we delineate the pathways through which nanoparticles can reach the brain and the subsequent health implications. There is growing evidence of a disturbing association between nanoparticle exposure and the onset of neurodegenerative conditions, highlighting the imperative for comprehensive research and strategic interventions. Gaining a deep understanding of these mechanisms and enacting protective policies are crucial steps toward reducing the health threats of nanoparticles, thereby maximizing their therapeutic advantages.

Development of a Flexible Sensor-Integrated Tissue Patch to Monitor Early Organ Rejection Processes Using Impedance Spectroscopy.

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.

Ultrastructural investigation of iron oxide nanoparticles accumulation in the liver of common carp (Cyprinus carpio Linnaeus, 1758).

In recent years, the intensive production of nanoparticles with a wide application has led to their transfer to the environment, including the water ecosystem. The accumulation of nanoparticles in fish, causing various pathological changes in the host, raises certain concerns. In the current study, we investigated the penetration and bioaccumulation of Fe3O4 nanoparticles, in the liver of common carp (Cyprinus carpio Linnaeus, 1758). Common carp juveniles were exposed to Fe3O4 nanoparticles at concentrations of 10 and 100 mg. After 7 days, their livers were examined by light and transmission electron microscopes. Compared to normal fish's liver, after using a small concentration (10 mg) of nanoparticles, changes were observed in erythrocytes, hepatocytes, intracellular canaliculi, and bile ducts of the liver. At a high concentration (100 mg), the intensity of changes increased significantly. The liver's capsule was damaged, and a considerable number of hepatocytes were completely destroyed. Additionally, the walls of blood vessels and biliary ductule walls was notably disturbed. It was found that the intensity of pathologies occurring in the liver, increases proportionally with higher concentrations of nanoparticles. Confirmation via electron microscopic methods revealed that Fe3O4 nanoparticles, when administered with food to common carp, enter the fish's liver through erythrocytes localized in the lumen of blood vessels. From there, they traverse through the endothelium of vessels, proceed to hepatocytes, including cytoplasmic organelles, intracellular canaliculi, biliary ductules, and eventually reach the bile ducts. Fe3O4 nanoparticles in all structural elements of fish liver was up to 20 nm. Therefore, high concentrations of nanoparticles in the environment harms the bodies of aquatic organisms, including fish. The changes identified in the liver of common carp in the present study are valuable information in assessing possible risks to other components of the aquatic ecosystem and organisms.

Secondary metabolites in topical infectious diseases and nanomedicine applications.

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.

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Effects of superparamagnetic iron oxide nanoparticles (SPIONS) testicular injection on Leydig cell function and sperm production in a murine model.

In the domain of medical advancement, nanotechnology plays a pivotal role, especially in the synthesis of biocompatible materials for therapeutic use. Superparamagnetic Iron Oxide Nanoparticles (SPIONs), known for their magnetic properties and low toxicity, stand at the forefront of this innovation. This study explored the reproductive toxicological effects of Sodium Citrate-functionalized SPIONs (Cit_SPIONs) in adult male mice, an area of research that holds significant potential yet remains largely unknown. Our findings reveal that Cit_SPIONs induce notable morphological changes in interstitial cells and the seminiferous epithelium when introduced via intratesticular injection. This observation is critical in understanding the interactions of nanomaterials within reproductive biological systems. A striking feature of this study is the rapid localization of Cit_SPIONs in Leydig cells post-injection, a factor that appears to be closely linked with the observed decrease in steroidogenic activity and testosterone levels. This data suggests a possible application in developing nanostructured therapies targeting androgen-related processes. Over 56 days, these nanoparticles exhibited remarkable biological distribution in testis parenchyma, infiltrating various cells within the tubular and intertubular compartments. While the duration of spermatogenesis remained unchanged, there were many Tunel-positive germ cells, a notable reduction in daily sperm production, and reduced progressive sperm motility in the treated group. These insights not only shed light on the intricate mechanisms of Cit_SPIONs interaction with the male reproductive system but also highlight the potential of nanotechnology in developing advanced biomedical applications.

Evaluation of the effects of zinc oxide (ZnO NPs) nanoparticles synthesized by green synthesis on Caenorhabditis elegans.

In recent years, the rapid development of nanotechnology has caused the products obtained with this technology to be used more daily. Information on the effects of these products, which provide great advantages in every respect, on human health and the environment is insufficient. It has been suggested that these nanoparticles may have toxic effects on living things, mostly in animal experiments and cell cultures. In this paper, the organism Caenorhabditis elegans (C. elegans), which contains a genome and biochemical ways highly similar to humans, is used to understand and reveal the metabolism of Zinc oxide nanoparticles (ZnO NPs) toxicological effects. The toxicological effects of ZnO NPs on C. elegans organisms were investigated and the results were evaluated in terms of environment and human health. C. elegans was exposed to commercial ZnO NPs and green synthesized ZnO NPs from Olea europaea (olive tree, OLE). LC50 values were determined by probit analysis (green synthesized ZnO NP LC5024h = 84.97 mg/L, LC5072h = 33.27 mg/L, commercial ZnO NPs LC5024h = 5.75 mg/L, LC5072h = 1.91 mg/L). When the survival times of C. elegans were evaluated by the Kaplan-Meier method, it was seen that commercial ZnO NPs were more toxic than green synthesized ZnO NPs. In MTT tests, it was clearly seen that commercial ZnO NPs and green synthesized ZnO NPs entered the cell and caused different cytotoxicity. While there was a difference between control and 0.5, 2.5, 5, 10, 25, and 50 mg/L doses in commercial ZnO NP applications, there were significant differences between control and 25, 50 mg/L concentrations in green synthesized ZnO NP applications.

Holotomography and atomic force microscopy: a powerful combination to enhance cancer, microbiology and nanotoxicology research.

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.

Exploring the interplay between the TGF-ßpathway and SLN-mediated transfection: implications for gene delivery efficiency in prostate cancer and non-cancer cells.

Solid lipid nanoparticles (SLN) are widely recognized for their biocompatibility, scalability, and long-term stability, making them versatile formulations for drug and gene delivery. Cellular interactions, governed by complex endocytic and signaling pathways, are pivotal for successfully applying SLN as a therapeutic agent. This study aims to enhance our understanding of the intricate interplay between SLN and cells by investigating the influence of specific endocytic and cell signaling pathways, with a focus on the impact of the TGF-ßpathway on SLN-mediated cell transfection in both cancerous and non-cancerous prostate cells. Here, we systematically explored the intricate mechanisms governing the interactions between solid lipid nanoparticles and cells. By pharmacologically manipulating endocytic and signaling pathways, we analyzed alterations in SLNplex internalization, intracellular traffic, and cell transfection dynamics. Our findings highlight the significant role of macropinocytosis in the internalization and transfection processes of SLNplex in both cancer and non-cancer prostate cells. Moreover, we demonstrated that the TGF-ßpathway is an important factor influencing endosomal release, potentially impacting gene expression and modulating cell transfection efficiency. This study provides novel insights into the dynamic mechanisms governing the interaction between cells and SLN, emphasizing the pivotal role of TGF-ßsignaling in SLN-mediated transfection, affecting internalization, intracellular transport, and release of the genetic cargo. These findings provide valuable insight for the optimization of SLN-based therapeutic strategies in prostate-related applications.