The impact and safety of encapsulated nanomaterials as a new alternative against carbapenem resistant bacteria. a systematic review.

The emergence of multi drug resistant bacterial infections has caused a critical problem with implication on hospitalization and mortality rates. This systematic review aims to review the combined antimicrobial effect of nanoparticles attached to the traditionally used antibiotics, to overcome the antibiotic resistance crisis. In this systematic search we focused on preclinical studies that have used animal models, to test and evaluate the effect of nanomaterials added to antibiotics against gram negative bacteria with carbapenem resistance. Where, this newly formed structure has led to significant decrease in bacterial load in animal model serum. Furthermore, by evaluating nanomaterial cytotoxicity and inflammatory markers, promising results were established, where low toxicity indices were presented, supporting the ability of this new pathway to be used as an alternative to abused antibiotics. Our research collected the various data and showed encouraging preclinical one for using nanomaterials with antibiotics. This undeniable route should be considered, due to its ability to contribute to the treatment of multi drug resistant bacterial infections. These findings provide base for future studies and reinforce the need for more evaluation and testing on the safety of nanomaterials against bacterial infections.

Machine Learning Models for Predicting Cytotoxicity of Nanomaterials.

The wide application of nanomaterials in consumer and medical products has raised concerns about their potential adverse effects on human health. Thus, more and more biological assessments regarding the toxicity of nanomaterials have been performed. However, the different ways the evaluations were performed, such as the utilized assays, cell lines, and the differences of the produced nanoparticles, make it difficult for scientists to analyze and effectively compare toxicities of nanomaterials. Fortunately, machine learning has emerged as a powerful tool for the prediction of nanotoxicity based on the available data. Among different types of toxicity assessments, nanomaterial cytotoxicity was the focus here because of the high sensitivity of cytotoxicity assessment to different treatments without the need for complicated and time-consuming procedures. In this review, we summarized recent studies that focused on the development of machine learning models for prediction of cytotoxicity of nanomaterials. The goal was to provide insight into predicting potential nanomaterial toxicity and promoting the development of safe nanomaterials.

Potential roles of Kruppel-like factors in mediating adverse vascular effects of nanomaterials: A review.

The development of nanotechnology leads to the exposure of human beings to nanomaterials (NMs), and there is a health concern about the adverse vascular effects of NMs. Current data from epidemiology, controlled human exposure, and animal studies suggested that exposure to NMs could induce cardiopulmonary effects. In support of in vivo findings, in vitro studies showed that direct contact of vascular cells with NMs could induce endothelial cell (EC) activation and promote macrophage foam cell formation, although only limited studies showed that NMs could damage vascular smooth muscle cells and promote their phenotypic switch. It has been proposed that NMs induced adverse vascular effects via different mechanisms, but it is still necessary to understand the upstream events. Kruppel-like factors (KLFs) are a set of C2H2 zinc finger transcription factors (TFs) that can regulate various aspects of vascular biology, but currently, the roles of KLF2 in mediating the adverse vascular effects of NMs have gained little attention by toxicologists. This review summarized current knowledge about the adverse vascular effects of NMs and proposed the potential roles of KLFs in mediating these effects based on available data from toxicological studies as well as the current understanding about KLFs in vascular biology. Finally, the challenges in investigating the role of KLFs in vascular toxicology were also summarized. Considering the important roles of KLFs in vascular biology, further studies are needed to understand the influence of NMs on KLFs and the downstream events.

Graphene Family Nanomaterials in Ocular Applications: Physicochemical Properties and Toxicity.

Graphene family nanomaterials (GFNs) are rapidly emerging for ocular applications due to their outstanding physicochemical properties. Since the eyes are very sensitive organs and the contact between the eyes and GFNs in eye drops, contact lenses, intraocular drug delivery systems and biosensors and even the workers handling these nanomaterials is inevitable, it is necessary to investigate their ocular toxicities and physiological interactions with cells as well as their toxicity mechanisms. The toxicity of GFNs can be extremely affected by their physicochemical properties, including composition, size, surface chemistry, and oxidation level as well as dose and the time of exposure. Up to now, there are several studies on the in vitro and in vivo toxicity of GFNs; however, a comprehensive review on ocular toxicity and applications of GFNs is missing, and a knowledge about the health risks of eye exposure to the GFNs is predominantly unspecified. This review highlights the ocular applications of GFNs and systematically covers the most recent advances of GFNs' physicochemical properties, in vitro and in vivo ocular toxicity, and the possible toxicity mechanisms as well as provides some perspectives on the potential risks of GFNs in material development and biomedical applications.

Investigating biological effects of multidimensional carboxylated carbon-based nanomaterials on human lung A549 cells revealed via non-targeted metabolomics approach.

The biological responses of multidimensional carboxylated carbon-based nanomaterials (c-CBNs), including carboxylated graphene, carbon nanotube, and fullerene, on human lung A549 cells were investigated by using metabolomics technology. The structure and components of c-CBNs were characterized, and their biological effects were evaluated through cell apoptosis and viability analysis. Additionally, the metabolomics analysis of the nanomaterial-cell interaction system was performed using the established platform combining liquid chromatography-mass spectrometry (LC-MS) with the bioinformatics system. Results revealed that all tested c-CBNs demonstrated some biological effects in our cell model. However, significant metabolomic alterations induced by c-CBNs were also observed mainly in amino acids, organic acids, glycerophospholipids, and glycerolipids. Further, under the tested concentrations, the multiple dimensions of c-CBNs played a major role in determining the metabolic process in various interaction modes. This study provides an advanced alternative for evaluating metabolic effects of multidimensional nanomaterials through metabolomics technology considering the association between dimension and metabolic characteristics.

The SCCS scientific advice on the safety of nanomaterials in cosmetics.

The Cosmetic Regulation (EC) No 1223/2009 specifically covers the risk of nanomaterials used in cosmetic products. If there are concerns regarding the safety of a nanomaterial, the European Commission refers it to the SCCS for a scientific opinion. The Commission mandated the SCCS to identify the scientific basis for safety concerns that could be used as a basis for identifying and prioritising nanomaterials for safety assessment, and to revisit previous inconclusive SCCS opinions on nanomaterials to identify any concerns for potential risks to the consumer health. The SCCS Scientific Advice identified the key general aspects of nanomaterials that should raise a safety concern for a safety assessor/manager, so that the nanomaterial(s) in question could be subjected to safety assessment to establish safety to the consumer. The Advice also developed a list of the nanomaterials notified to the Commission for use in cosmetics in an order of priority for safety assessment, and revisited three previous inconclusive opinions on nanomaterials to highlight concerns over consumer safety that merited further safety assessment.

Regulatory landscape of nanotechnology and nanoplastics from a global perspective.

Nanotechnology and more particularly nanotechnology-based products and materials have provided a huge potential for novel solutions to many of the current challenges society is facing. However, nanotechnology is also an area of product innovation that is sometimes developing faster than regulatory frameworks. This is due to the high complexity of some nanomaterials, the lack of a globally harmonised regulatory definition and the different scopes of regulation at a global level. Research organisations and regulatory bodies have spent many efforts in the last two decades to cope with these challenges. Although there has been a significant advancement related to analytical approaches for labelling purposes as well as to the development of suitable test guidelines for nanomaterials and their safety assessment, there is a still a need for greater global collaboration and consensus in the regulatory field. Furthermore, with growing societal concerns on plastic litter and tiny debris produced by degradation of littered plastic objects, the impact of micro- and nanoplastics on humans and the environment is an emerging issue. Despite increasing research and initial regulatory discussions on micro- and nanoplastics, there are still knowledge gaps and thus an urgent need for action. As nanoplastics can be classified as a specific type of incidental nanomaterials, current and future scientific investigations should take into account the existing profound knowledge on nanotechnology/nanomaterials when discussing issues around nanoplastics. This review was conceived at the 2019 Global Summit on Regulatory Sciences that took place in Stresa, Italy, on 24-26 September 2019 (GSRS 2019) and which was co-organised by the Global Coalition for Regulatory Science Research (GCRSR) and the European Commission's (EC) Joint Research Centre (JRC). The GCRSR consists of regulatory bodies from various countries around the globe including EU bodies. The 2019 Global Summit provided an excellent platform to exchange the latest information on activities carried out by regulatory bodies with a focus on the application of nanotechnology in the agriculture/food sector, on nanoplastics and on nanomedicines, including taking stock and promoting further collaboration. Recently, the topic of micro- and nanoplastics has become a new focus of the GCRSR. Besides discussing the challenges and needs, some future directions on how new tools and methodologies can improve the regulatory science were elaborated by summarising a significant portion of discussions during the summit. It has been revealed that there are still some uncertainties and knowledge gaps with regard to physicochemical properties, environmental behaviour and toxicological effects, especially as testing described in the dossiers is often done early in the product development process, and the material in the final product may behave differently. The harmonisation of methodologies for quantification and risk assessment of nanomaterials and micro/nanoplastics, the documentation of regulatory science studies and the need for sharing databases were highlighted as important aspects to look at.

Adverse cardiovascular responses of engineered nanomaterials: Current understanding of molecular mechanisms and future challenges.

Nanotechnology is spanning multiple fields of study from materials science to computer engineering and drug discovery. Since the early 21st century, nanotechnology and nano-enabled research have received great attention and governmental funding accompanied with interest to ensure human and environmental safety of engineered nanomaterials (ENMs). Optimal functioning of the cardiovascular (CV) system is of utmost importance for the overall health of the body. Following exposure, ENMs essentially end up in the circulation (at least partially) and hence it is key to assess any associated adverse CV consequences. Accumulating research suggests that exposure to ENMs (different compositions and physicochemical properties) has the capacity to directly and indirectly interact with CV components resulting in adverse events and worsening of CV complications. However, the underlying molecular mechanisms driving these events remain to be elucidated. In this article, we review state-of-art literature on ENM-associated adverse CV responses and discuss the potential underlying molecular mechanisms.

Effectiveness of Nanohydroxyapatite on Demineralization of Enamel and Cementum Surrounding Margin of Yttria-Stabilized Zirconia Polycrystalline Ceramic Restoration.

INTRODUCTION: Prosthetic dentistry has shifted toward prevention of caries occurrence surrounding restorative margin through the anti-demineralization process. This study examines the ability of nanohydroxyapatite (NHA) gel and Clinpro (CP) on enhancing resistance to demineralization of enamel and cementum at margin of restoration. MATERIALS AND METHODS: Thirty extracted mandibular third molars were segregated at 1 mm above and below cementoenamel junction (CEJ) to separate CEJ portions and substituted with zirconia disks by bonding to crown and root portions with resin adhesive. The enamel and cementum area of 4 × 4 mm2 neighboring zirconia was applied with either NHA or CP, while one group was left no treatment (NT) before demineralized with carbopal. Vickers hardness (VHN) of enamel and cementum was evaluated before material application (B M), after material application (A M), and after demineralization (A D). Analysis of variance (ANOVA) and post hoc multiple comparisons were used to justify for the significant difference (α = 0.05). Scanning electron microscopy (SEM) and X-ray diffraction (XRD) were determined for surface evaluations. RESULTS: The mean ± SD of VHN for B M, A M, and A D for enamel and cementum was 393.24 ± 26.27, 392.89 ± 17.22, 155.00 ± 5.68 and 69.89 ± 4.59, 66.28 ± 3.61, 18.13 ± 0.54 for NT groups, respectively, 390.10 ± 17.69, 406.77 ± 12.86, 181.55 ± 7.99 and 56.01 ± 9.26, 62.71 ± 6.15, 19.09 ± 1.16 for NHA groups, respectively, and 387.90 ± 18.07, 405.91 ± 9.83, 188.95 ± 7.43 and 54.68 ± 7.30, 61.81 ± 4.30, 19.22 ± 1.25 for CP groups, respectively. ANOVA indicated a significant increase in anti-demineralization of enamel and cementum upon application of NHA or CP (p < 0.05). Multiple comparisons indicated the capability in inducing surface strengthening to resist demineralization for enamel and cementum of NHA which was comparable to CP (p > 0.05) as evidenced by SEM and XRD data indicating NHA and CP deposition and crystallinity accumulation. CONCLUSION: NHA and CP were capable of enhancing anti-demineralization for enamel and cementum. The capability in resisting the demineralization process of NHA was comparable with CP. NHA was highly recommended for anti-demineralization for enamel and cementum surrounding restorative margin.

A Review on Conventional and Advanced Methods for Nanotoxicology Evaluation of Engineered Nanomaterials.

Nanotechnology can be defined as the field of science and technology that studies material at nanoscale (1-100 nm). These nanomaterials, especially carbon nanostructure-based composites and biopolymer-based nanocomposites, exhibit excellent chemical, physical, mechanical, electrical, and many other properties beneficial for their application in many consumer products (e.g., industrial, food, pharmaceutical, and medical). The current literature reports that the increased exposure of humans to nanomaterials could toxicologically affect their environment. Hence, this paper aims to present a review on the possible nanotoxicology assays that can be used to evaluate the toxicity of engineered nanomaterials. The different ways humans are exposed to nanomaterials are discussed, and the recent toxicity evaluation approaches of these nanomaterials are critically assessed.

Characterisation of Engineered Nanomaterials in Nano-Enabled Products Exhibiting Priority Environmental Exposure.

Analytical limitations have constrained the determination of nanopollution character from real-world sources such as nano-enabled products (NEPs), thus hindering the development of environmental safety guidelines for engineered nanomaterials (ENMs). This study examined the properties of ENMs in 18 commercial products: sunscreens, personal care products, clothing, and paints-products exhibiting medium to a high potential for environmental nanopollution. It was found that 17 of the products contained ENMs; 9, 3, 3, and 2 were incorporated with nTiO2, nAg, binaries of nZnO + nTiO2, and nTiO2 + nAg, respectively. Commonly, the nTiO2 were elongated or angular, whereas nAg and nZnO were near-spherical and angular in morphology, respectively. The size ranges (width × length) were 7-48 × 14-200, 34-35 × 37-38, and 18-28 nm for nTiO2, nZnO, and nAg respectively. All ENMs were negatively charged. The total concentration of Ti, Zn, and Ag in the NEPs were 2.3 × 10-4-4.3%, 3.4-4.3%, and 1.0 × 10-4-11.3 × 10-3%, respectively. The study determined some key ENM characteristics required for environmental risk assessment; however, challenges persist regarding the accurate determination of the concentration in NEPs. Overall, the study confirmed NEPs as actual sources of nanopollution; hence, scenario-specific efforts are recommended to quantify their loads into water resources.

Nano-SAR Modeling for Predicting the Cytotoxicity of Metal Oxide Nanoparticles to PaCa2.

Nowadays, the impact of engineered nanoparticles (NPs) on human health and environment has aroused widespread attention. It is essential to assess and predict the biological activity, toxicity, and physicochemical properties of NPs. Computation-based methods have been developed to be efficient alternatives for understanding the negative effects of nanoparticles on the environment and human health. Here, a classification-based structure-activity relationship model for nanoparticles (nano-SAR) was developed to predict the cellular uptake of 109 functionalized magneto-fluorescent nanoparticles to pancreatic cancer cells (PaCa2). The norm index descriptors were employed for describing the structure characteristics of the involved nanoparticles. The Random forest algorithm (RF), combining with the Recursive Feature Elimination (RFE) was employed to develop the nano-SAR model. The resulted model showed satisfactory statistical performance, with the accuracy (ACC) of the test set and the training set of 0.950 and 0.966, respectively, demonstrating that the model had satisfactory classification effect. The model was rigorously verified and further extensively compared with models in the literature. The proposed model could be reasonably expected to predict the cellular uptakes of nanoparticles and provide some guidance for the design and manufacture of safer nanomaterials.

Brave new world revisited: Focus on nanomedicine.

Nanomedicine is at a crossroads: with relatively few success stories in terms of clinical translation despite more and more research on increasingly sophisticated nanomaterials, it is important to consider whether we are on the right track. Indeed, it is crucial that we address the fact that while considerable efforts are being made to overcome barriers to translation from the bench to the clinic, scientists are still struggling to decipher fundamental aspects of nanomaterial interactions with biological systems. We believe that a key to the successful adoption of nanomedicines in oncology and beyond lies in a deeper understanding of underlying biological processes and in decoding interactions between engineered nanomaterials and biological systems. Here we provide an overview of progress in nanomedicine during the past 5 years.

Tissue Specific Fate of Nanomaterials by Advanced Analytical Imaging Techniques - A Review.

A variety of imaging and analytical methods have been developed to study nanoparticles in cells. Each has its benefits, limitations, and varying degrees of expense and difficulties in implementation. High-resolution analytical scanning transmission electron microscopy (HRSTEM) has the unique ability to image local cellular environments adjacent to a nanoparticle at near atomic resolution and apply analytical tools to these environments such as energy dispersive spectroscopy and electron energy loss spectroscopy. These tools can be used to analyze particle location, translocation and potential reformation, ion dispersion, and in vivo synthesis of second-generation nanoparticles. Such analyses can provide in depth understanding of tissue-particle interactions and effects that are caused by the environmental "invader" nanoparticles. Analytical imaging can also distinguish phases that form due to the transformation of "invader" nanoparticles in contrast to those that are triggered by a response mechanism, including the commonly observed iron biomineralization in the form of ferritin nanoparticles. The analyses can distinguish ion species, crystal phases, and valence of parent nanoparticles and reformed or in vivo synthesized phases throughout the tissue. This article will briefly review the plethora of methods that have been developed over the last 20 years with an emphasis on the state-of-the-art techniques used to image and analyze nanoparticles in cells and highlight the sample preparation necessary for biological thin section observation in a HRSTEM. Specific applications that provide visual and chemical mapping of the local cellular environments surrounding parent nanoparticles and second-generation phases are demonstrated, which will help to identify novel nanoparticle-produced adverse effects and their associated mechanisms.

Advanced In Vitro Testing Strategies and Models of the Intestine for Nanosafety Research.

There is growing concern about the potential adverse effects of oral exposure to engineered nanomaterials (ENM). Recent years have witnessed major developments in and advancement of intestinal in vitro models for nanosafety evaluation. The present paper reviews the key factors that should be considered for inclusion in nonanimal alternative testing approaches to reliably reflect the in vivo dynamics of the physicochemical properties of ENM as well the intestinal physiology and morphology. Currently available models range from simple cell line-based monocultures to advanced 3D systems and organoids. In addition, in vitro approaches exist to replicate the mucous barrier, digestive processes, luminal flow, peristalsis, and interactions of ENM with the intestinal microbiota. However, while the inclusion of a multitude of individual factors/components of particle (pre)treatment, exposure approach, and cell model approximates in vivo-like conditions, such increasing complexity inevitably affects the system's robustness and reproducibility. The selection of the individual modules to build the in vitro testing strategy should be driven and justified by the specific purpose of the study and, not least, the intended or actual application of the investigated ENM. Studies that address health hazards of ingested ENM likely require different approaches than research efforts to unravel the fundamental interactions or toxicity mechanisms of ENM in the intestine. Advanced reliable and robust in vitro models of the intestine, especially when combined in an integrated testing approach, offer great potential to further improve the field of nanosafety research.

Energy Storage Materials as Emerging Nano-contaminants.

New and emerging nanotechnologies are increasingly using nanomaterials that undergo significant chemical reactions upon exposure to environmental conditions. The rapid advent of lithium ion batteries for energy storage in mobile electronics and electric vehicles is leading to rapid increases in the manufacture of complex transition metal oxides that incorporate elements such as Co and Ni that have the potential for significant adverse biological impact. This Perspective summarizes some of the important technological drivers behind complex oxide materials and highlights some of the chemical transformations that need to be understood in order to assess the overall environmental impact associated with energy storage technologies.

Nanomaterials and Innate Immunity: A Perspective of the Current Status in Nanosafety.

Human exposure to engineered nanomaterials (ENMs) is inevitable due to the plethora of applications for which they are being manufactured and integrated within. ENMs demonstrate plentiful advantages in terms of industrial approaches as well as from a consumer perspective. However, despite such positives, doubts remain over the human health implications of ENM exposure. In light of the increased research focus upon the potential effects of ENM exposure to human health in recent decades, questions still remain regarding the safety of these highly advanced, precision-tuned physical entities. The risk of short-term, high-dose exposure to humans is considered relatively low, although this has formed the direction of the hazard-assessment community since the turn of the 21st century. However, the possibility of humans being exposed repeatedly over a long period of time to a low-dose of ENMs of varying physicochemical characteristics is of significant concern, and thus, industry, government, academic, and consumer agencies are only now beginning to consider this. Notably, when considering the human health implications of such low-dose, long-term, repeated exposure scenarios, the impact of ENMs upon the human immune system is of primary importance. However, there remains a real need to understand the impact of ENMs upon the human immune system, especially the innate immune system, at all stages of life, given exposure to nanosized particles begins before birth, that is, of the fetus. Therefore, the purpose of this perspective is to summarize what is currently known regarding ENM exposure of different components of the innate immune system and identify knowledge gaps that should be addressed if we are to fully deduce the impact of ENM exposure on innate immune function.

Neurotoxicology of Nanomaterials.

The remarkable advances coming about through nanotechnology promise to revolutionize many aspects of modern life; however, these advances come with a responsibility for due diligence to ensure that they are not accompanied by adverse consequences for human health or the environment. Many novel nanomaterials (having at least one dimension <100 nm) could be highly mobile if released into the environment and are also very reactive, which has raised concerns for potential adverse impacts including, among others, the potential for neurotoxicity. Several lines of evidence led to concerns for neurotoxicity, but perhaps none more than observations that inhaled nanoparticles impinging on the mucosal surface of the nasal epithelium could be internalized into olfactory receptor neurons and transported by axoplasmic transport into the olfactory bulbs without crossing the blood-brain barrier. From the olfactory bulb, there is concern that nanomaterials may be transported deeper into the brain and affect other brain structures. Of course, people will not be exposed to only engineered nanomaterials, but rather such exposures will occur in a complex mixture of environmental materials, some of which are incidentally generated particles of a similar inhalable size range to engineered nanomaterials. To date, most experimental studies of potential neurotoxicity of nanomaterials have not considered the potential exposure sources and pathways that could lead to exposure, and most studies of nanomaterial exposure have not considered potential neurotoxicity. Here, we present a review of potential sources of exposures to nanoparticles, along with a review of the literature on potential neurotoxicity of nanomaterials. We employ the linked concepts of an aggregate exposure pathway (AEP) and an adverse outcome pathway (AOP) to organize and present the material. The AEP includes a sequence of key events progressing from material sources, release to environmental media, external exposure, internal exposure, and distribution to the target site. The AOP begins with toxicant at the target site causing a molecular initiating event and, like the AEP, progress sequentially to actions at the level of the cell, organ, individual, and population. Reports of nanomaterial actions are described at every key event along the AEP and AOP, except for changes in exposed populations that have not yet been observed. At this last stage, however, there is ample evidence of population level effects from exposure to ambient air particles that may act similarly to engineered nanomaterials. The data give an overall impression that current exposure levels may be considerably lower than those reported experimentally to be neurotoxic. This impression, however, is tempered by the absence of long-term exposure studies with realistic routes and levels of exposure to address concerns for chronic accumulation of materials or damage. Further, missing across the board are "key event relationships", which are quantitative expressions linking the key events of either the AEP or the AOP, making it impossible to quantitatively project the likelihood of adverse neurotoxic effects from exposure to nanomaterials or to estimate margins of exposure for such relationships.

Exploring Flow Cytometry-Based Micronucleus Scoring for Reliable Nanomaterial Genotoxicity Assessment.

The increased use of engineered nanomaterials (ENM) such as SiO2 and TiO2 in industrial products, especially in food, raises concerns with regard to their effect on human health. In particular, ENM-induced genotoxicity is crucial to investigate, since DNA damage can cause induction or promotion of carcinogenesis. However, current in vitro and in vivo nanogenotoxicological data are highly contradictory, which impedes interpretation and extrapolation. Hence, robust, reliable, and ideally scalable in vitro methods for nanogenotoxicity assessment are of great interest. This work aimed at evaluating the suitability of flow cytometry-based micronuclei scoring for reliable nanogenotoxicological assessment in human intestinal cells. Therefore, we have evaluated the genotoxicity of differently sized SiO2 and TiO2 from different sources (food-relevant, commercially available, and laboratory-synthesized) using the well-established alkaline single cell gel electrophoresis (Comet assay) and the micronucleus (MN) assay employing a flow cytometric readout. Our study demonstrates that physiologically relevant doses of several types of SiO2 and TiO2 did not cause genotoxicity, as assessed by the Comet assay, and the MN flow cytometry assay under the particular experimental conditions described. To improve data reliability, we identified ENM-induced interferences with flow cytometric scoring employing a set of interference controls, which is generally applicable for any nanomaterial and any cell line. In conclusion, flow cytometry-based MN scoring appears to be a promising methodology in nanogenotoxicity testing since data acquisition and analysis are significantly faster, highly scalable in terms of throughput, and less operator-dependent compared to the traditional microscopic evaluation. In particular, ENM-induced false-positive or false-negative results, which have not been addressed sufficiently in the literature, can be detected easily, thus enhancing data reliability.

Safety Assessment of Nanomaterials for Antimicrobial Applications.

The interplay between nanotechnology and pathogens offers a new quest to fight against human infections. Inspiring from their unique thermal, magnetic, optical, or redox potentials, numerous nanomaterials have been employed for bacterial theranostics. The past decade has seen dramatic progress in the development of various nanoantimicrobials, which demands more focus on their safety assessment. The present review critically discusses the toxicity of nanoantimicrobials and the role of key features, including composition, size, surface charge, loading capability, hydrophobicity/philicity, precise release, and functionalization, that can contribute to modulating the effects on microbes. Moreover, how differences in microbe's structure, biofilm formation, persistence cells, and intracellular pathogens bestow resistance or sensitivity toward nanoantimicrobials is broadly investigated. In extension, the most important types of nanoantimicrobial with clinical prospective and their safety assessment are summarized, and finally, based on available evidence, an insight of the principles in designing safer nanoantimicrobials for overcoming pathogens and future challenges in the field is provided.