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Extracellular vesicles (EVs), natural membrane-bound structures released by cells, offer a promising platform for precise and targeted delivery of therapeutic payloads, including drugs and nanoparticles. This comprehensive review explores the integration of engineered nanomaterials with EVs to advance drug delivery systems. It covers various aspects of this integration, including techniques for synthesizing, loading, characterizing, and applying nanomaterials within EVs. Methodologies for integrating diverse nanocarriers like nanoparticles, liposomes, and quantum dots into EVs are discussed, along with characterization methods such as electron microscopy and light scattering. Attention is also given to considerations of biological compatibility, safety assessments, and strategies for surface modification to enhance targeting precision. Highlighting various applications, including targeted drug delivery, cancer therapy, and vaccine development, the review underscores the potential of EV-nanomaterial hybrids to leverage EVs' innate targeting capabilities and the versatility of nanomaterials. However, it also addresses challenges such as scalability, standardization, and safety that must be overcome to facilitate the clinical translation of these promising biomedical solutions. [ABSTRACT FROM AUTHOR]

Engineered nanomaterials, such as nanoparticles, nanocomposites and chalcogenides, possess distinct characteristics as a result of their extremely small size, leading to significant advancements in industries such as healthcare, electronics and energy. Nanomaterials play a crucial role in cancer immunotherapy by greatly improving the effectiveness of several treatments, including immune checkpoint inhibitors, T cell transfer therapy, monoclonal antibodies and therapeutic vaccines. They achieve this by enhancing drug transport and increasing targeting accuracy. Although they have the ability to bring about significant changes, obstacles, such as potential toxicity, environmental effect and manufacturing complexity, impede their widespread use. In order to address these problems, it is crucial to use tactics such as thorough biocompatibility testing, environmentally friendly production procedures and modern manufacturing technology. This study examines the progress and difficulties in using synthetic nanomaterials for cancer immunotherapy and suggests ways to ensure their safe and efficient incorporation into medical treatments. [ABSTRACT FROM AUTHOR]

This manuscript presents a multiomics investigation into the metabolic and proteomic responses of wheat to molybdenum (Mo)- and copper (Cu)-based engineered nanomaterials (ENMs) exposure via root and leaf application methods. Wheat plants underwent a four-week growth period with a 16 h photoperiod (light intensity set at 150 μmol·m-2·s-1), at 22 °C and 60% humidity. Six distinct treatments were applied, including control conditions alongside exposure to Mo- and Cu-based ENMs through both root and leaf routes. The exposure dosage amounted to 6.25 mg of the respective element per plant. An additional treatment with a lower dose (0.6 mg Mo/plant) of Mo ENM exclusively through the root system was introduced upon the detection of phytotoxicity. Utilizing LC-MS/MS analysis, 82 metabolites across various classes and 24 proteins were assessed in different plant tissues (roots, stems, leaves) under diverse treatments. The investigation identified 58 responsive metabolites and 19 responsive proteins for Cu treatments, 71 responsive metabolites, and 24 responsive proteins for Mo treatments, mostly through leaf exposure for Cu and root exposure for Mo. Distinct tissue-specific preferences for metabolite accumulation were revealed, highlighting the prevalence of organic acids and fatty acids in stem or root tissues, while sugars and amino acids were abundant in leaves, mirroring their roles in energy storage and photosynthesis. Joint-pathway analysis was conducted and unveiled 23 perturbed pathways across treatments. Among these, Mo exposure via roots impacted all identified pathways, whereas exposure via leaf affected 15 pathways, underscoring the reliance on exposure route of metabolic and proteomic responses. The coordinated response observed in protein and metabolite concentrations, particularly in amino acids, highlighted a dynamic and interconnected proteomic-to-metabolic-to-proteomic relationship. Furthermore, the contrasting expression patterns observed in glutamate dehydrogenase (upregulation at 1.38 ≤ FC ≤ 1.63 with high Mo dose, and downregulation at 0.13 ≤ FC ≤ 0.54 with low Mo dose) and its consequential impact on glutamine expression (7.67 ≤ FC ≤ 39.60 with high Mo dose and 1.50 ≤ FC ≤ 1.95 with low Mo dose) following Mo root exposure highlighted dose-dependent regulatory trends influencing proteins and metabolites. These findings offer a multidimensional understanding of plant responses to ENMs exposure, guiding agricultural practices and environmental safety protocols while advancing knowledge on nanomaterial impacts on plant biology.

Abstract Background Modulating the microbiome with nanomaterials has been proposed to improve plant growth, and reduce reliance on external inputs. Carbon Nanosol (CNS) was attracted for its potential to improve plant productivity. However, the mechanism between CNS and rhizosphere microorganisms remained largely elusive. Results Here, we tried to systematically explore the effects of CNS (600 and 1200 mg/L by concentration) on tobacco growth, soil physical properties, and root-associated microbiome. The influence of CNS on soil physicochemical properties and plant growth was significant and dose-dependent, leading to a 28.82% increase in biomass accumulation by 600 mg/L CNS. Comparison between the CNS-treated and control plants revealed significant differences in microbiome composition, including 1148 distinct ASVs (923 bacteria and 225 fungi), microbiome interactions, and metabolic function of root-associated microbiomes. Fungal and bacterial communities had different response patterns for CNS treatment, with phased and dose-dependent effects, with the most significant changes in microbial community structure observed at 1200 mg/L after 10 days of treatment. Microbial networks of CNS-treated plants had more nodes and edges, higher connectivity, and more hub microorganisms than those of control plants. Compared with control, CNS significantly elevated abundances of various bacterial biomarkers (such as Sphingomonas and Burkholderia) and fungi biomarkers (including Penicillium, Myceliophthora, and Talaromyces), which were potential plant-beneficial organisms. Functional prediction based on metagenomic data demonstrated pathways related to nutrient cycling being greatly enriched under CNS treatment. Furthermore, 391 culturable bacteria and 44 culturable fungi were isolated from soil and root samples. Among them, six bacteria and two fungi strains enriched upon CNS treatment were validated to have plant growth promotion effect, and two fungi (Cladosporium spp. and Talaromyces spp.) played their roles by mediating volatile organic compounds (VOCs). To some extent, the driving and shaping of the microbiome by CNS contributed to its impact on plant growth and development. Conclusion Our results revealed the key role of root-associated microbiota in mediating the interaction between CNS and plants, thus providing valuable insights and strategies for harnessing CNS to enhance plant growth. Graphical Abstract

Background: Modulating the microbiome with nanomaterials has been proposed to improve plant growth, and reduce reliance on external inputs. Carbon Nanosol (CNS) was attracted for its potential to improve plant productivity. However, the mechanism between CNS and rhizosphere microorganisms remained largely elusive. Results: Here, we tried to systematically explore the effects of CNS (600 and 1200 mg/L by concentration) on tobacco growth, soil physical properties, and root-associated microbiome. The influence of CNS on soil physicochemical properties and plant growth was significant and dose-dependent, leading to a 28.82% increase in biomass accumulation by 600 mg/L CNS. Comparison between the CNS-treated and control plants revealed significant differences in microbiome composition, including 1148 distinct ASVs (923 bacteria and 225 fungi), microbiome interactions, and metabolic function of root-associated microbiomes. Fungal and bacterial communities had different response patterns for CNS treatment, with phased and dose-dependent effects, with the most significant changes in microbial community structure observed at 1200 mg/L after 10 days of treatment. Microbial networks of CNS-treated plants had more nodes and edges, higher connectivity, and more hub microorganisms than those of control plants. Compared with control, CNS significantly elevated abundances of various bacterial biomarkers (such as Sphingomonas and Burkholderia) and fungi biomarkers (including Penicillium, Myceliophthora, and Talaromyces), which were potential plant-beneficial organisms. Functional prediction based on metagenomic data demonstrated pathways related to nutrient cycling being greatly enriched under CNS treatment. Furthermore, 391 culturable bacteria and 44 culturable fungi were isolated from soil and root samples. Among them, six bacteria and two fungi strains enriched upon CNS treatment were validated to have plant growth promotion effect, and two fungi (Cladosporium spp. and Talaromyces spp.) played their roles by mediating volatile organic compounds (VOCs). To some extent, the driving and shaping of the microbiome by CNS contributed to its impact on plant growth and development. Conclusion: Our results revealed the key role of root-associated microbiota in mediating the interaction between CNS and plants, thus providing valuable insights and strategies for harnessing CNS to enhance plant growth. [ABSTRACT FROM AUTHOR]

Engineered nanomaterials (ENMs) have a broad array of applications in agriculture, engineering, manufacturing, and medicine. Decades of toxicology research have demonstrated that ENMs can cause genotoxic effects on bacteria, mammalian cells, and animals. Some metallic ENMs (MENMs), e.g., metal or metal oxide nanoparticles TiO2 and CuO, induce genotoxicity via direct DNA damage and/or reactive oxygen species-mediated indirect DNA damage. There are various physical features of MENMs that may play an important role in promoting their genotoxicity, for example, size and chemical composition. For a valid genotoxicity assessment of MENMs, general considerations should be given to various factors, including, but not limited to, NM characterization, sample preparation, dosing selection, NM cellular uptake, and metabolic activation. The recommended in vitro genotoxicity assays of MENMs include hprt gene mutation assay, chromosomal aberration assay, and micronucleus assay. However, there are still knowledge gaps in understanding the mechanisms underlying the genotoxicity of MENMs. There are also a variety of challenges in the utilization and interpretation of the genotoxicity assessment assays of MENMs. In this review article, we provide mechanistic insights into the genotoxicity of MENMs in the human environment. We review advances in applying new endpoints, biomarkers, and methods to the genotoxicity assessments of MENMs. The guidance of the United States, the United Kingdom, and the European Union on the genotoxicity assessments of MENMs is also discussed. [ABSTRACT FROM AUTHOR]

Occupational safety and health (OSH) can be relevant in achieving the United Nation's Sustainable Development Goal of decent work by 2030. However, further OSH actions are needed. This paper identifies the role of OSH in addressing two of many determinants of decent work.: new forms of work/innovative technologies and worker aging. The authors conducted a discursive analysis of the two determinants and provided examples for consideration. New forms of work and innovative technologies can not only promote but also undermine the future of decent work, and unhealthy aging impedes longer working lives. With a focus on the OSH aspects of new jobs, innovative technologies, and aging, decent work is more likely to be achieved. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs), natural membrane-bound structures released by cells, offer a promising platform for precise and targeted delivery of therapeutic payloads, including drugs and nanoparticles. This comprehensive review explores the integration of engineered nanomaterials with EVs to advance drug delivery systems. It covers various aspects of this integration, including techniques for synthesizing, loading, characterizing, and applying nanomaterials within EVs. Methodologies for integrating diverse nanocarriers like nanoparticles, liposomes, and quantum dots into EVs are discussed, along with characterization methods such as electron microscopy and light scattering. Attention is also given to considerations of biological compatibility, safety assessments, and strategies for surface modification to enhance targeting precision. Highlighting various applications, including targeted drug delivery, cancer therapy, and vaccine development, the review underscores the potential of EV-nanomaterial hybrids to leverage EVs’ innate targeting capabilities and the versatility of nanomaterials. However, it also addresses challenges such as scalability, standardization, and safety that must be overcome to facilitate the clinical translation of these promising biomedical solutions.

The editorial discusses the use of nanomaterials and nanostructures in cancer and pathogenic infection diagnosis and therapy. It covers various topics such as advanced nanoparticles in clinical trials, combining engineered nanomaterials with extracellular vesicles for drug delivery, boron nitride nanotubes as drug carriers, ibuprofen-loaded chitosan nanoparticles for pulmonary therapy, and hybrid nanostructures for modern therapy. The review emphasizes the potential of nanotechnology to improve therapeutic efficacy and safety, calling for continued interdisciplinary collaboration and innovation in the field. [Extracted from the article]

Hazard assessment is the first step in evaluating the potential adverse effects of chemicals. Traditionally, toxicological assessment has focused on the exposure, overlooking the impact of the exposed system on the observed toxicity. However, systems toxicology emphasizes how system properties significantly contribute to the observed response. Hence, systems theory states that interactions store more information than individual elements, leading to the adoption of network based models to represent complex systems in many fields of life sciences. Here, they develop a network‐based approach to characterize toxicological responses in the context of a biological system, inferring biological system specific networks. They directly link molecular alterations to the adverse outcome pathway (AOP) framework, establishing direct connections between omics data and toxicologically relevant phenotypic events. They apply this framework to a dataset including 31 engineered nanomaterials with different physicochemical properties in two different in vitro and one in vivo models and demonstrate how the biological system is the driving force of the observed response. This work highlights the potential of network‐based methods to significantly improve their understanding of toxicological mechanisms from a systems biology perspective and provides relevant considerations and future data‐driven approaches for the hazard assessment of nanomaterials and other advanced materials. [ABSTRACT FROM AUTHOR]

Abstract Adverse Outcome Pathways (AOPs) have been proposed to facilitate mechanistic understanding of interactions of chemicals/materials with biological systems. Each AOP starts with a molecular initiating event (MIE) and possibly ends with adverse outcome(s) (AOs) via a series of key events (KEs). So far, the interaction of engineered nanomaterials (ENMs) with biomolecules, biomembranes, cells, and biological structures, in general, is not yet fully elucidated. There is also a huge lack of information on which AOPs are ENMs-relevant or -specific, despite numerous published data on toxicological endpoints they trigger, such as oxidative stress and inflammation. We propose to integrate related data and knowledge recently collected. Our approach combines the annotation of nanomaterials and their MIEs with ontology annotation to demonstrate how we can then query AOPs and biological pathway information for these materials. We conclude that a FAIR (Findable, Accessible, Interoperable, Reusable) representation of the ENM-MIE knowledge simplifies integration with other knowledge. Scientific contribution This study introduces a new database linking nanomaterial stressors to the first known MIE or KE. Second, it presents a reproducible workflow to analyze and summarize this knowledge. Third, this work extends the use of semantic web technologies to the field of nanoinformatics and nanosafety.

Introduction: Due to uncertainties regarding the risks of engineered nanomaterials for human health and the environment, different organizations and researchers have developed various management frameworks and assessment tools to mitigate hazards during the procedures and applications of engineered nanomaterials. However, most of these techniques do not meet all the individual requirements. This study provides a review and introduction to the techniques developed for the management of safety, health, and environmental risks associated with engineered nanomaterials. Material and Methods: In order to find pertinent documents on the safe handling of engineered nanomaterials, a search was conducted using the following keywords: “Engineered nanomaterials”, “Framework”, “Tool”, “Risk management”, “Occupational exposure”, “Environment”, “Risk assessment”, and “Nanotechnology”. The search was conducted on various databases, including Scopus, Web of Science, NIOSH, ECHA, and ISO. Among the search results, tools and frameworks that specifically focus on the safety, health, and environmental risk management or assessment of engineered nanomaterials were selected. Results: Among the search results, 17 frameworks and 11 developments in the field of managing occupational, environmental, and toxicological risks associated with engineered nanomaterials were discussed. Various frameworks and tools for identifying, evaluating, and managing the potential risks of engineered nanomaterials vary in terms of their scope, goals, risk assessment approaches, and output, offering diverse applications. Conclusion: Various tools and frameworks, each with unique properties, applications, and limitations, can assist organizations in achieving their goals related to safety, health, and environmental issues in the field of nanotechnology. Currently, there is no consensus on the optimal approach for assessing the risks of nanomaterials, underscoring the necessity for additional research, development, and collaboration in this field.

The increasing demand for durable, eco-friendly clothing has led to the use of nanomaterials in textiles. However, concerns arise about the impact of engineered nanomaterials (ENMs). Studies have explored nanoparticle release from textiles during usage and washing. However, the existing data is fragmented, and a comprehensive grasp is absent. A systematic review is required to consolidate existing evidence and offer a thorough analysis of nanoparticle release from nano-enhanced textiles in commercial use and washing. This review assess the research aims to concerning the release of nanomaterials from commercial textiles during usage and laundering. The process involved defining objectives, crafting a search strategy, utilizing databases, and applying inclusion/exclusion criteria. After deduplication, articles were screened for eligibility, covering nanoparticle characteristics and release mechanisms. Searches spanned Scopus, PubMed, and Web of Science, using keywords like "Nano," "Nanoparticles," etc. Original articles on nanomaterial release from conventional textiles were included. Out of 1549 articles identified, and met the criteria for inclusion in the study. The results reveal that textiles employing nanotechnology can indeed release a significant quantity of nanoparticles. The characteristics of these released particles, including their quantity and composition, are influenced by various factors such as nanoparticle structure, adhesive properties, fabric type, and environmental interactions. While there exist variations between laboratory simulations and real-world conditions, these findings underscore potential risks associated with nanoparticle release, underscoring the necessity for toxicological assessments and additional research into particle behavior, particularly emphasizing the functional aspects of fibers and the environmental impact following nanoparticle release after washing. [ABSTRACT FROM AUTHOR]

Engineered nanomaterials have emerged as a promising technology for water treatment, particularly for removing heavy metals. Their unique physicochemical properties enable them to adsorb large quantities of metals even at low concentrations. This review explores the efficacy of various nanomaterials, including zeolites, polymers, chitosan, metal oxides, and metals, in removing heavy metals from water under different conditions. Functionalization of nanomaterials is a strategy to enhance their separation, stability, and adsorption capacity. Experimental parameters such as pH, adsorbent dosage, temperature, contact time, and ionic strength significantly influence the adsorption process. In comparison, engineered nanomaterials show promise for heavy metal remediation, but several challenges exist, including aggregation, stability, mechanical strength, long-term performance, and scalability. Furthermore, the potential environmental and health impacts of nanomaterials require careful consideration. Future research should focus on addressing these challenges and developing sustainable nanomaterial-based remediation strategies. This will involve interdisciplinary collaboration, adherence to green chemistry principles, and comprehensive risk assessments to ensure the safe and effective deployment of nanomaterials in heavy metal remediation at both lab and large-scale levels. [ABSTRACT FROM AUTHOR]

Adverse Outcome Pathways (AOPs) have been proposed to facilitate mechanistic understanding of interactions of chemicals/materials with biological systems. Each AOP starts with a molecular initiating event (MIE) and possibly ends with adverse outcome(s) (AOs) via a series of key events (KEs). So far, the interaction of engineered nanomaterials (ENMs) with biomolecules, biomembranes, cells, and biological structures, in general, is not yet fully elucidated. There is also a huge lack of information on which AOPs are ENMs-relevant or -specific, despite numerous published data on toxicological endpoints they trigger, such as oxidative stress and inflammation. We propose to integrate related data and knowledge recently collected. Our approach combines the annotation of nanomaterials and their MIEs with ontology annotation to demonstrate how we can then query AOPs and biological pathway information for these materials. We conclude that a FAIR (Findable, Accessible, Interoperable, Reusable) representation of the ENM-MIE knowledge simplifies integration with other knowledge. Scientific contribution: This study introduces a new database linking nanomaterial stressors to the first known MIE or KE. Second, it presents a reproducible workflow to analyze and summarize this knowledge. Third, this work extends the use of semantic web technologies to the field of nanoinformatics and nanosafety. [ABSTRACT FROM AUTHOR]

Sustainable agriculture, essential for global food security, calls for innovative methods to improve crop yields and conserve resources. Nanopriming, utilizing nanoparticles to enhance seed germination and growth, builds preresistance to diseases and reduces dependence on pesticides and fertilizers. Here, we address two major challenges in the field: effects of varying nanoparticle sizes on seed nutrient enhancement and the lack of efficient, automated systems for germination monitoring. Focusing on zinc oxide (ZnO) nanoparticles, we synthesize them using hydrothermal and solvothermal methods. Our experiments on bitter gourd (Momordica charantia) and red amaranth (Amaranthus gangeticus) show that nanopriming with these particles, especially those smaller than 30 nm, significantly improves seed germination and seedling growth. Specifically, we observe up to a 23% increase in germination and a 40% rise in shoot length for bitter gourd and a 43% increase in germination with a 20% boost in shoot length for red amaranth. Nanopriming at a concentration of 150 mg/L significantly enhances bitter gourd plant growth, with a notable 90% increase in height and 74% increase in leaf count compared to hydroprimed plants, showcasing the positive impact on fresh biomass production. For field-level monitoring, we propose a sophisticated smart monitoring system incorporating a custom-designed two-axis CNC machine with a single-board computer and high-resolution camera to redefine seed germination and growth assessment. [ABSTRACT FROM AUTHOR]

Engineered silver nanoparticles (AgNPs), including silver silicate nanoparticles (Ag-SiO2 NPs), are used in a wide variety of medical and consumer applications. Inhaled AgNPs have been found to translocate to the olfactory bulb (OB) after inhalation and intranasal instillation. However, the biological effects of Ag-SiO2 NPs and their potential nose-to-brain transport have not been evaluated. The present study assessed whether inhaled Ag-SiO2 NPs can elicit microglial activation in the OB. Adult Sprague-Dawley rats inhaled aerosolized Ag-SiO2 NPs at a concentration of 1 mg/ml for 6 hours. On day 0, 1, 7, and 21 post-exposure, rats were necropsied and OB were harvested. Immunohistochemistry on OB tissues were performed with anti-ionized calcium-binding adapter molecule 1 and heme oxygenase-1 as markers of microglial activation and oxidative stress, respectively. Aerosol characterization indicated Ag-SiO2 NPs were sufficiently aerosolized with moderate agglomeration and high-efficiency deposition in the nasal cavity and olfactory epithelium. Findings suggested that acute inhalation of Ag-SiO2 NPs elicited transient and differential microglial activation in the OB without significant microglial recruitment or oxidative stress. The delayed and differential pattern of microglial activation in the OB implied that inhaled Ag-SiO2 may have translocated to the central nervous system via intra-neuronal pathways.

Engineered nanomaterials (ENMs) have a broad array of applications in agriculture, engineering, manufacturing, and medicine. Decades of toxicology research have demonstrated that ENMs can cause genotoxic effects on bacteria, mammalian cells, and animals. Some metallic ENMs (MENMs), e.g., metal or metal oxide nanoparticles TiO2 and CuO, induce genotoxicity via direct DNA damage and/or reactive oxygen species-mediated indirect DNA damage. There are various physical features of MENMs that may play an important role in promoting their genotoxicity, for example, size and chemical composition. For a valid genotoxicity assessment of MENMs, general considerations should be given to various factors, including, but not limited to, NM characterization, sample preparation, dosing selection, NM cellular uptake, and metabolic activation. The recommended in vitro genotoxicity assays of MENMs include hprt gene mutation assay, chromosomal aberration assay, and micronucleus assay. However, there are still knowledge gaps in understanding the mechanisms underlying the genotoxicity of MENMs. There are also a variety of challenges in the utilization and interpretation of the genotoxicity assessment assays of MENMs. In this review article, we provide mechanistic insights into the genotoxicity of MENMs in the human environment. We review advances in applying new endpoints, biomarkers, and methods to the genotoxicity assessments of MENMs. The guidance of the United States, the United Kingdom, and the European Union on the genotoxicity assessments of MENMs is also discussed.

With the rapid development of engineered nanomaterials (ENMs) in biomedical applications, their biocompatibility and cytotoxicity need to be evaluated properly. Recently, it has been demonstrated that inflammasome activation may be a vital contributing factor for the development of biological responses induced by ENMs. Among the inflammasome family, NLRP3 inflammasome has received the most attention because it directly interacts with ENMs to cause the inflammatory effects. However, the pathways that link ENMs to NLRP3 inflammasome have not been thoroughly summarized. Thus, we reviewed recent findings on the role of major ENMs properties in modulating NLRP3 inflammasome activation, both in vitro and in vivo, to provide a better understanding of the underlying mechanisms. In addition, the interactions between ENMs and NLRP3 inflammasome activation are summarized, which may advance our understanding of safer designs of nanomaterials and ENM-induced adverse health effects.

Engineered nanomaterials have emerged as a promising technology for water treatment, particularly for removing heavy metals. Their unique physicochemical properties enable them to adsorb large quantities of metals even at low concentrations. This review explores the efficacy of various nanomaterials, including zeolites, polymers, chitosan, metal oxides, and metals, in removing heavy metals from water under different conditions. Functionalization of nanomaterials is a strategy to enhance their separation, stability, and adsorption capacity. Experimental parameters such as pH, adsorbent dosage, temperature, contact time, and ionic strength significantly influence the adsorption process. In comparison, engineered nanomaterials show promise for heavy metal remediation, but several challenges exist, including aggregation, stability, mechanical strength, long-term performance, and scalability. Furthermore, the potential environmental and health impacts of nanomaterials require careful consideration. Future research should focus on addressing these challenges and developing sustainable nanomaterial-based remediation strategies. This will involve interdisciplinary collaboration, adherence to green chemistry principles, and comprehensive risk assessments to ensure the safe and effective deployment of nanomaterials in heavy metal remediation at both lab and large-scale levels.

Production and use of engineered nanomaterials have grown substantially in recent years, leading to an increased potential for occupational exposure to these materials. Health and safety data remain largely unknown or incomplete for most engineered nanomaterials. The management of possible risks associated with engineered nanomaterials in the workplace is of paramount importance for workers, employers, and occupational health and safety (OHS) professionals and is a complex and developing field of research. A key component of risk management is the effective communication of known and potential risks in the workplace. Many proposals and recommendations have been made for signage to warn of the location and use of engineered nanomaterials within occupational settings. Such signage could raise awareness and serve as a reminder of the potential unknown health and safety risks presented by engineered nanomaterials. We have designed a simple visual pictogram intended to indicate the presence of engineered nanomaterials in the workplace. Herein, we present our pictogram in contrast with those concomitantly identified in various scientific guidelines and literature, provide details on a pilot-scale evaluation of this signage administered before a recent institution-level adaptation, and provide recommendations for those interested in implementing this signage in other workplaces. Strengthening risk communication by adapting this visual warning pictogram could help draw attention to potential risks, improve workplace hygiene, and ideally, decrease occupational exposure for those working with engineered nanomaterials. [ABSTRACT FROM AUTHOR]

Although engineered nanomaterials (ENMs) have tremendous potential to generate technological benefits in numerous sectors, uncertainty on the risks of ENMs for human health and the environment may impede the advancement of novel materials. Traditionally, the risks of ENMs can be evaluated by experimental methods such as environmental field monitoring and animal-based toxicity testing. However, it is time-consuming, expensive, and impractical to evaluate the risk of the increasingly large number of ENMs with the experimental methods. On the contrary, with the advancement of artificial intelligence and machine learning, in silico methods have recently received more attention in the risk assessment of ENMs. This review discusses the key progress of computational nanotoxicology models for assessing the risks of ENMs, including material flow analysis models, multimedia environmental models, physiologically based toxicokinetics models, quantitative nanostructure–activity relationships, and meta-analysis. Several challenges are identified and a perspective is provided regarding how the challenges can be addressed. [ABSTRACT FROM AUTHOR]

The increasing use of molybdenum disulfide (MoS2) nanoparticles (NPs) raises concerns regarding their accumulation in soil ecosystems, with limited studies on their impact on soil organisms. Study aim: To unravel the effects of MoS2 nanosheets (two-dimensional (2D) MoS2 NPs) and bulk MoS2 (156, 313, 625, 1250, 2500 mg/kg) on Enchytraeus crypticus and Folsomia candida. The organisms' survival and avoidance behavior remained unaffected by both forms, while reproduction and DNA integrity were impacted. For E. crypticus, the individual endpoint reproduction was more sensitive, increasing at lower concentrations of bulk MoS2 and decreasing at higher ones and at 625 mg/kg of 2D MoS2 NPs. For F. candida, the molecular endpoint DNA integrity was more impacted: 2500 mg/kg of bulk MoS2 induced DNA damage after 2 days, with all concentrations inducing damage by day 7. 2D MoS2 NPs induced DNA damage at 156 and 2500 mg/kg after 2 days, and at 1250 and 2500 mg/kg after 7 days. Despite affecting the same endpoints, bulk MoS2 induced more effects than 2D MoS2 NPs. Indeed, 2D MoS2 NPs only inhibited E. crypticus reproduction at 625 mg/kg and induced fewer (F. candida) or no effects (E. crypticus) on DNA integrity. This study highlights the different responses of terrestrial organisms to 2D MoS2 NPs versus bulk MoS2, reinforcing the importance of risk assessment when considering both forms. [ABSTRACT FROM AUTHOR]

In the last 50 years, various frameworks have been used to control and manage potentially toxic chemical risks; however, these chemicals continue to negatively impact environmental and human health. This work was intended to provide a systematic review of the literature on essential aspects of current risk management frameworks for potentially toxic chemicals. The frameworks were reviewed using Organisation for Economic Co-operation and Development (OECD) principles that focus on elements, successes, shortcomings, similarities, and dissimilarities premised on the experiences of many countries. Keywords such as heavy metals, health risk, industrial chemicals, potentially toxic elements, chemical pollutants, and risk management framework were utilised to search the literature from databases and other sources. Ten risk framework documents selected from an initial yield of 1349 using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow processes met the inclusion criteria. The key elements of risk frameworks that were identified included the risk assessment paradigm, iteration, tiered approach, weight of evidence, uncertainty analysis, and multi-criteria decision analysis among others. Notable gaps in risk frameworks that required improvements to effectively manage health risks posed by potentially toxic chemicals were identified. While existing risk frameworks have made significant contributions to human health and environmental protection, new and comprehensive frameworks are needed to address the novel and dynamic risks posed by toxic industrial chemicals. Also, there is a need to promote the use of risk management frameworks in developing countries through technology transfer and the provision of financial assistance to improve environmental and public health protection from toxic chemicals. [ABSTRACT FROM AUTHOR]

Delivery of proteins into walled plant cells remains a challenge with few tractable solutions. Recent advances in biomacromolecule delivery using nanotechnology may evince methods to be exploited for protein delivery. While protein delivery remains no small feat, even in mammalian systems, the ability for nanoparticles to penetrate the cell wall and be decorated with a plethora of functional moieties makes them ideal protein vehicles in plants. As advances in protein biotechnology accelerate, so does the need for commensurate delivery systems. However, the road to nanoparticle-mediated protein delivery is fraught with challenges in regard to cell wall penetration, intracellular delivery, endosomal escape, and nanoparticle chemistry and design. The dearth of literature surrounding protein delivery in walled plant cells hints at the challenge of this problem but also indicates vast opportunity for innovations in plant-tailored nanotechnology.

Biomedical applications of nanomaterials, especially in diagnosing, management, and treatment of diseases are evolving. However, nanotoxicity remains a major challenge in availing the full biomedical potential of engineered nanomaterials. Nevertheless, recent advancements in the field have suggested that smart engineering of targeting ligands and presence of biomolecules on the surface of nanomaterials can reduce nanotoxicity through differential affinity, enhanced biocompatibility, and efficient internalization. Further, certain ligand-functionalized nanomaterials permit their tracking in cells and tissues over a prolonged period of time, making them suitable for nanomedicine applications. In this seminal review, a range of strategies, which have been employed for surface functionalization of nanomaterials using various biomolecules that confer amide / hydrazone bonds, thiol binding, and surface silanization have been evaluated. The challenges, and impact of surface functionalization of nanomaterials on cellular uptake, drug targeting, molecular imaging, and biocompatibility are also discussed. Finally, nanotoxicity aspects and recommendations of ligand-based surface engineered nanomaterials are detailed for future biomedical applications.

Nanotechnology is employed across a wide range of antibacterial applications in clinical settings, food, pharmaceutical and textile industries, water treatment and consumer goods. Depending on type and concentration, engineered nanomaterials (ENMs) can also benefit bacteria in myriad contexts including within the human body, in biotechnology, environmental bioremediation, wastewater treatment, and agriculture. However, to realize the full potential of nanotechnology across broad applications, it is necessary to understand conditions and mechanisms of detrimental or beneficial effects of ENMs to bacteria. To study ENM effects, bacterial population growth or viability are commonly assessed. However, such endpoints alone may be insufficiently sensitive to fully probe ENM effects on bacterial physiology. To reveal more thoroughly how bacteria respond to ENMs, molecular-level omics methods such as transcriptomics, proteomics, and metabolomics are required. Because omics methods are increasingly utilized, a body of literature exists from which to synthesize state-of-the-art knowledge. Here we review relevant literature regarding ENM impacts on bacterial cellular pathways obtained by transcriptomic, proteomic, and metabolomic analyses across three growth and viability effect levels: inhibitory, sub-inhibitory or stimulatory. As indicated by our analysis, a wider range of pathways are affected in bacteria at sub-inhibitory vs. inhibitory ENM effect levels, underscoring the importance of ENM exposure concentration in elucidating ENM mechanisms of action and interpreting omics results. In addition, challenges and future research directions of applying omics approaches in studying bacterial-ENM interactions are discussed.

Recently, the scope, regulation, legislation, and metrology of the analytical chemistry of engineered nanomaterials (ENMs) have been reviewed in the Part 1 of the IUPAC Technical Report. Chemical analysis of nanomaterials in complex sample matrices presents a substantial challenge for analytical science and regulatory agencies. The purpose of the present Part 2 is to discuss the detection, characterization, and quantification of nanomaterials in samples of complex matrices including methods for sample preparation and fitness for purpose. Analytical methods applied to analysis in matrices of environmental samples, food, cosmetics, and biological samples as well as those used to monitor the fate of ENMs in the environment and biological systems are reported. Tables of numerous recently published works on analyses of typical ENMs with detailed protocols and conclusive comments are presented. There is a rapid development in the field mostly in the stage of accumulation of factual material. The single-particle inductively coupled plasma mass spectrometry is already widely used at the chemical analysis of metal-containing nanoparticles. [ABSTRACT FROM AUTHOR]

The widespread and increasing use of engineered nanomaterials (i.e., particulate materials measuring 1–100 nanometers (nm) in at least one dimension) poses a potential health and safety risk to exposed workers. The unique properties of nanomaterials have made nanomaterials useful in multiple industries. However, their production and use may compromise worker health, presenting an emerging occupational health hazard, the acute and chronic effects of which have not been fully assessed. In this scoping review, we critically assess the literature on biomarkers of effect from nanoparticles and discuss the utility of biomonitoring as a means of assessing the physiological effects of nanoparticle exposure among nanotechnology workers. Multiple databases were queried based on select inclusion and exclusion criteria according to PRISMA guidelines, and articles were independently screened by two topic experts. Of 286 articles initially retrieved, 28 were included after screening and eligibility. The reviewed articles indicated that sensitive effect biomarkers could reflect early health effects of exposure to nanoparticles in the workplace and may be useful for monitoring toxicological effects and associated risks. [ABSTRACT FROM AUTHOR]

The growing production and application of engineered nanomaterials (ENM) in everyday products make their environmental discharge increasingly likely. This risk is particularly elevated at the end of the useful life of ENM. Given the lack of regulations targeting the safe disposal of ENM at end-of-life, nanowaste (NW) currently follows conventional waste management pathways even though their potential adverse effects on humans and the natural environment are well documented in the literature. Presently, preference exists for treating NW via centralized waste-to-energy systems such as incineration, given the potentially hazardous nature of NW. In this work, a Design of experiment (DOE) methodology—Box Behnken design was employed to optimize three independent operating parameters of a pilot-scale scrubber concerning the collection of nanoparticles under waste incineration conditions. The pilot-scale scrubber was designed and operated to be representative of a full-scale spray scrubber found in a hazardous waste incineration plant. The independent parameters studied are; the gas flowrate, the liquid flowrate and the droplet diameter. Six responses were chosen corresponding to the nanoparticle collection efficiencies at particle sizes in the diffusion-dominant, intermediate and impaction-dominant regions. The experimental results were analyzed for statistical significance using Design Expert software (V13). The DOE model by the software was then used to predict optimum operating conditions with maximum nanoparticle collection. A maximum nanoparticle collection efficiency of 41–60% was predicted by the DOE model under optimal conditions of a gas flowrate of 46.1 Nm3 h−1, a liquid flowrate of 4.8 L min−1, and a droplet diameter of 60 µm. These optimal conditions were determined by the highest liquid flowrate, the smallest droplet diameter, and a gas flowrate near the middle of the range studied. The results of the confirmatory experiments (43–62%) at the optimum combination agreed with the predicted data. The experimental results were also found to be in good agreement when compared to a mechanistic model based on impaction, Brownian diffusion and interception collection mechanisms. [ABSTRACT FROM AUTHOR]

The toxicity of engineered nanomaterials (ENMs) in vivo and in vitro has formed the basis of most studies. However, the toxicity of ENMs, particularly on the immune system, i.e. immunotoxicity, and their role in manipulating it, are less known. This review addresses the initiation or exacerbation as well as the attenuation of allergic asthma by a variety of ENMs and how they may be used in drug delivery to enhance the treatment of asthma. This review also highlights a few research gaps in the study of the immunotoxicity of ENMs, for example, the potential drawbacks of assays used in immunotoxicity assays; the potential role of hormesis during dosing of ENMs; and the variables that result in discrepancies among different studies, such as the physicochemical properties of ENMs, differences in asthmatic animal models, and different routes of administration. Abbreviations: AHR: airway hyperresponsiveness; ALI: air-lung epithelium interface; BDP: beclometasone dipropionate; CB: carbon black; CNTs: carbon nanotubes; CpG: cytosine linked through a phosphodiester to guanine; EGFR: epidermal growth factor receptor; ENMs: engineered nanomaterials; GLA: gut--lung axis; Ig: immunoglobulin; IL: interleukin; LC: liquid crystalline; LLNA: local lymph node assay; LPS: lipopolysaccharide; MWCNTs: multi-walled CNTs; NPs: nanoparticles; OVA: ovalbumin; PAMAM: polyamidoamine; PFC: plaque-forming cell; PM: particulate matter; ROS: reactive oxygen species; SBS: salbutamol sulfate; SWCNTs: single-walled CNTs; TDI: toluene diisocyanate; VEGF: vascular endothelial growth factor [ABSTRACT FROM AUTHOR]

Nanotechnology is enjoying an impressive growth and the global nanotechnology industry is expected to exceed US$ 125 billion by 2024. Based on these successes, there are notions that enough is known and efforts on engineered nanomaterial environmental health and safety (nano-EHS) research should be put on the back burner. However, there are recent events showing that it is not the case. The US Food and Drug Administration found ferumoxytol (carbohydrate-coated superparamagnetic iron oxide nanoparticle) for anemia treatment could induce lethal anaphylactic reactions. The European Union will categorize TiO2 as a category 2 carcinogen due to its inhalation hazard and France banned use of TiO2 (E171) in food from January 1, 2020 because of its carcinogenic potential. Although nanoindustry is seemingly in a healthy state, growth could be hindered for the lack of certainty and more nano-EHS research is needed for the sustainable growth of nanoindustry. Herein, the current knowledge gaps and the way forward are elaborated.

Abstract Background The widespread use of new engineered nanomaterials (ENMs) in industries such as cosmetics, electronics, and diagnostic nanodevices, has been revolutionizing our society. However, emerging studies suggest that ENMs present potentially toxic effects on the human lung. In this regard, we developed a machine learning (ML) nano-quantitative-structure-toxicity relationship (QSTR) model to predict the potential human lung nano-cytotoxicity induced by exposure to ENMs based on metal oxide nanoparticles. Results Tree-based learning algorithms (e.g., decision tree (DT), random forest (RF), and extra-trees (ET)) were able to predict ENMs’ cytotoxic risk in an efficient, robust, and interpretable way. The best-ranked ET nano-QSTR model showed excellent statistical performance with R2 and Q2-based metrics of 0.95, 0.80, and 0.79 for training, internal validation, and external validation subsets, respectively. Several nano-descriptors linked to the core-type and surface coating reactivity properties were identified as the most relevant characteristics to predict human lung nano-cytotoxicity. Conclusions The proposed model suggests that a decrease in the ENMs diameter could significantly increase their potential ability to access lung subcellular compartments (e.g., mitochondria and nuclei), promoting strong nano-cytotoxicity and epithelial barrier dysfunction. Additionally, the presence of polyethylene glycol (PEG) as a surface coating could prevent the potential release of cytotoxic metal ions, promoting lung cytoprotection. Overall, the current work could pave the way for efficient decision-making, prediction, and mitigation of the potential occupational and environmental ENMs risks.

Dhananjay Yadav,1,* Nidhi Puranik,2,* Anju Meshram,3,* Vishal Chavda,4 Peter Chang-Whan Lee,5 Jun-O Jin6 1Department of Life Science, Yeungnam University, Gyeongsan, 38541, South Korea; 2Biological Sciences Department, Bharathiar University, Coimbatore, Tamil Nadu, 641046, India; 3Department of Biotechnology, Kalinga University, Naya Raipur, Chhattisgarh, India; 4Department of Pathology, Stanford School of Medicine, Stanford University Medical Center, Stanford, CA, 94305, USA; 5Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, South Korea; 6Department of Microbiology, University of Ulsan College of Medicine, Seoul, 05505, South Korea*These authors contributed equally to this workCorrespondence: Peter Chang-Whan Lee, Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, South Korea, Email pclee@amc.seoul.kr Jun-O Jin, Department of Microbiology, University of Ulsan College of Medicine, Seoul, 05505, South Korea, Email junojin@amc.seoul.krAbstract: Cancer is a broad term for a group of diseases involving uncontrolled cell growth and proliferation. There is no cure for cancer despite recent significant improvements in screening, treatment, and prevention approaches. Among the available treatments, immunotherapy has been successful in targeting and killing cancer cells by stimulating or enhancing the body’s immune system. Antibody-based immunotherapeutic agents that block immune checkpoint proteins expressed by cancer cells have shown promising results. The rapid development of nanotechnology has contributed to improving the effectiveness and reducing the adverse effects of these anti-cancer immunotherapeutic agents. Recently, engineered nanomaterials have been the focus of many state-of-The-art approaches toward effective cancer treatment. In this review, the contribution of various nanomaterials such as polymeric nanoparticles, dendrimers, microspheres, and carbon nanomaterials in improving the efficiency of anti-cancer immunotherapy is discussed as well as nanostructures applied to combination cancer immunotherapy.Keywords: nanotechnology, combination therapy, cancer therapy, engineered nanomaterials, nanotoxicity, synergistic therapy

The incorporation of engineered nanomaterials (ENMs) in biomedical and consumer products has been growing, leading to increased human exposure. Previous research was largely focused on studying direct ENM toxicity in unrealistic high-exposure settings. This could result in overlooking potential adverse responses at low and subtoxic exposure levels. This study investigated adverse cellular outcomes to subtoxic concentrations of zinc oxide (ZnONPs) or nickel oxide (NiONPs) nanoparticles in the Raw 264.7 cells, a macrophage-like cell model. Exposure to both nanoparticles resulted in a concentration-dependent reduction of cell viability. A subtoxic concentration of 6.25 µg/mL (i.e., no observed adverse effect level) was used in subsequent experiments. Exposure to both nanoparticles at subtoxic levels induced reactive oxygen species generation. Cellular internalization data demonstrated significant uptake of NiONPs, while there was minimal uptake of ZnONPs, suggesting a membrane-driven interaction. Although subtoxic exposure to both nanoparticles was not associated with cell activation (based on the expression of MHC-II and CD86 surface markers), it resulted in the modulation of the lipopolysaccharide-induced inflammatory response (TNFα and IL6), and cells exposed to ZnONPs had reduced cell phagocytic capacity. Furthermore, subtoxic exposure to the nanoparticles distinctly altered the levels of several cellular metabolites involved in cell bioenergetics. These findings suggest that exposure to ENMs at subtoxic levels may not be devoid of adverse health outcomes. This emphasizes the importance of establishing sensitive endpoints of exposure and toxicity beyond conventional toxicological testing. [ABSTRACT FROM AUTHOR]

[Display omitted] In recent years, an increasing number of diverse Engineered Nano-Materials (ENMs), such as nanoparticles and nanotubes, have been included in many technological applications and consumer products. The desirable and unique properties of ENMs are accompanied by potential hazards whose impacts are difficult to predict either qualitatively or in a quantitative and predictive manner. Alongside established methods for experimental and computational characterisation, physics-based modelling tools like molecular dynamics are increasingly considered in Safe and Sustainability-by-design (SSbD) strategies that put user health and environmental impact at the centre of the design and development of new products. Hence, the further development of such tools can support safe and sustainable innovation and its regulation. This paper stems from a community effort and presents the outcome of a four-year-long discussion on the benefits, capabilities and limitations of adopting physics-based modelling for computing suitable features of nanomaterials that can be used for toxicity assessment of nanomaterials in combination with data-based models and experimental assessment of toxicity endpoints. We review modern multiscale physics-based models that generate advanced system-dependent (intrinsic) or time- and environment-dependent (extrinsic) descriptors/features of ENMs (primarily, but not limited to nanoparticles, NPs), with the former being related to the bare NPs and the latter to their dynamic fingerprinting upon entering biological media. The focus is on (i) effectively representing all nanoparticle attributes for multicomponent nanomaterials, (ii) generation and inclusion of intrinsic nanoform properties, (iii) inclusion of selected extrinsic properties, (iv) the necessity of considering distributions of structural advanced features rather than only averages. This review enables us to identify and highlight a number of key challenges associated with ENMs' data generation, curation, representation and use within machine learning or other advanced data-driven models to ultimately enhance toxicity assessment. Finally, the set up of dedicated databases as well as the development of grouping and read-across strategies based on the mode of action of ENMs using omics methods are identified as emerging methodologies for safety assessment and reduction of animal testing. [ABSTRACT FROM AUTHOR]