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Proposed scheme of internalization pathways of differently sized AuNPs with or without PCs by RAW 264.7 and Hep G2 cells. Reprinted with permission from [25]. Copyright (2015) American Chemical Society.

Proposed scheme of internalization pathways of differently sized AuNPs with or without PCs by RAW 264.7 and Hep G2 cells. Reprinted with permission from [25]. Copyright (2015) American Chemical Society.

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Nanoparticles (NPs) exposed to a biological milieu will strongly interact with proteins, forming “coronas” on the surfaces of the NPs. The protein coronas (PCs) affect the properties of the NPs and provide a new biological identity to the particles in the biological environment. The characterization of NP-PC complexes has attracted enormous researc...

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... studies have suggested that the effect of PCs on cellular uptake is also dependent on the size of the NPs. As differently sized AuNPs interact with cells via different endocytic pathways (Figure 9), FBS-coated 50 nm AuNPs show a significant inhibitory effect on the cellular uptake into the mouse leukemic monocyte macrophage cell line RAW 264.7 and human hepatocellular carcinoma cell line HepG2, whereas FBS-coated 20 or 2 nm AuNPs show almost no effect on the cellular uptake into both cell lines [25]. In the presence of a serum corona, silica NPs (SNPs) of 50, 100, and 200 nm diameters exhibit tremendous reductions in their uptake into M1 and M2 macrophages, in comparison with those in the absence of serum corona. ...

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... This multifaceted composition contributes to the stability and biocompatibility of the synthesized nanoparticles, enhancing their suitability for various applications [41]. This discrepancy underscores the importance of considering the corona layer in nanoparticle characterization and its potential influence on nanoparticle properties and behavior, which could also have implications for their antibacterial activity [34,42]. The significance of the biological corona surrounding NPs has been extensively studied and documented in the literature [42,43]. ...
... This discrepancy underscores the importance of considering the corona layer in nanoparticle characterization and its potential influence on nanoparticle properties and behavior, which could also have implications for their antibacterial activity [34,42]. The significance of the biological corona surrounding NPs has been extensively studied and documented in the literature [42,43]. This corona layer forms around NPs during synthesis, often originating from the biological components present in the synthesis medium. ...
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The continuous evolution and significance of green resources-based nanomaterials have spurred the exploration of sustainable sources for nanoparticle production. Green synthesis routes offer eco-friendly methodologies, ensuring nanoparticle stability and monodispersity, enhancing their efficiency for various applications. Notably, the thick biological corona layer surrounding nanoparticles (NPs) synthesized through green routes contributes to their unique properties. Consequently, there has been a surge in the development of NPs synthesis methods utilizing medicinal plants and diverse agricultural and waste resources. This study highlights the sustainable potential of barley grains for the synthesis of gold nanoparticles (Barley-AuNPs) and silver nanoparticles (Barley-AgNPs) as an environmentally friendly alternative, followed by NPs characterizations and their application against pathogenic bacteria: Escherichia coli UTI 89 and Pseudomonas aeruginosa PAO1. The rapid synthesis of Barley-AuNPs within 20 min and Barley-AgNPs within 30 min at 90 °C underscores the efficiency of barley as a green precursor. Characterization through advanced techniques, including SEM, TEM, EDS, AFM, DLS, FT-IR, MALDI-TOF, and sp-ICPMS, reveals the 20–25 nm size for Barley-AuNPs, while Barley-AgNPs demonstrate 2–10 nm size with spherical monodispersity. A notable contribution lies in the stability of these NPs over extended periods, attributed to a thick biological corona layer. This corona layer, which enhances stability, also influences the antimicrobial activity of Barley-AgNPs, presenting an intriguing trade-off. The antimicrobial investigations highlight the significant potential of Barley-AgNPs, with distinct minimum bactericidal concentrations (MBC) against P. aeruginosa and E. coli at 8 µg/mL. Overall, this research pioneers the use of barley grains for nanoparticle synthesis and unveils these nanoparticles' unique characteristics and potential antibacterial applications, contributing to the evolving landscape of sustainable nanotechnology. Graphic Abstract
... Dose and material size are among the main causes of all these adverse effects. The size of NPs can alter toxicity, and smallerdiameter NPs are more dangerous to cells than larger-diameter NPs, as smaller particles are more likely to reach intracellular sites such as mitochondria and nucleus Li & Lee, 2020). In addition, the cytotoxicity of NPs may be increased when they are mixed with different types of compounds. ...
Article
"Nano", which derives from the Latin word nanus and means dwarf, refers to a very small unit of measurement equal to one billionth of a meter. Nanotechnology, which deals with the manipulation of matter at the atomic and molecular level, has an application area in animal husbandry as well as in many fields. Nano-sized feed additives, which have come to the forefront in the livestock sector in recent years, have become an innovative application used to increase the nutritional value of feeds and optimize animal health and performance. Since these additives are nano-sized particles with increased specific surface area, they can have a positive effect on a number of factors such as digestibility, nutrient absorption, immune system, growth and development. Minerals in the form of nanoparticles used as feed additives can increase bioavailability by passing through the intestinal wall to body cells faster compared to larger particles. The nano level of the substance not only increases the productivity of animals, but also brings the potential to improve the functionality of feed molecules. Nano feed additives increase the digestion and absorption of feed, allowing animals to benefit from feed more effectively. However, there are several challenges associated with this approach. These include the potential for endotoxin production, reduced nutrient absorption due to interaction with natural nutrients, the possibility of nanoparticle accumulation in the animal body, health risks, ethical considerations, environmental concerns and some negative effects such as interference with natural nutrients that can be avoided by encapsulation. This article discusses recent studies on nano-sized feed additives that offer potential benefits in animal nutrition.
... Next, we briefly discuss the process of corona formation around an NP. Several recent reviews [41][42][43] are recommended for a more detailed presentation of this subject. The following section examines the RBC interaction with corona-coated NPs. ...
... The mechanism of hemolysis induced by NPPS has not yet been defined, but it nevertheless has to be NP adhesion-dependent so that changes in RBC/NP interaction conditions will modulate the level of cell hemolysis. Thus, the destabilization of the RBC membrane [40] by the interaction of NP with the cell lipid bilayer may activate membrane defects [41,42] that cause RBC hemolysis, implying that the attenuation of NP adhesion to RBC can reduce the hemolysis. ...
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The potential use of nanomaterials in medicine offers opportunities for novel therapeutic approaches to treating complex disorders. For that reason, a new branch of science named nanotoxicology, which aims to study the dangerous effects of nanomaterials on human health and on the environment, has recently emerged. However, the toxicity and risk associated with nanomaterials are unclear or not completely understood. The development of an adequate experimental strategy for assessing the toxicity of nanomaterials may include a rapid/express method that will reliably, quickly, and cheaply make an initial assessment. One possibility is the characterization of the hemocompatibility of nanomaterials, which includes their hemolytic activity as a marker. In this review, we consider various factors affecting the hemolytic activity of nanomaterials and draw the reader's attention to the fact that the formation of a protein corona around a nanoparticle can significantly change its interaction with the red cell. This leads us to suggest that the nanomaterial hemolytic activity in the buffer does not reflect the situation in the blood plasma. As a recommendation, we propose studying the hemocompatibility of nanomaterials under more physiologically relevant conditions, in the presence of plasma proteins in the medium and under mechanical stress.
... Electrophoretic Mobility (EM) Used to determine the zeta potential, which is a measure or estimation of the colloidal stability. [31,99,100] ...
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In the quest to effectively diagnose and treat the diseases that afflict mankind, the development of a tool capable of simultaneous detection and treatment would provide a significant cornerstone for the survival and control of these diseases. Theranostics denotes a portmanteau of therapeutics and diagnostics which simultaneously detect and treat ailments. Research advances have initiated the advent of theranostics in modern medicine. Overall, theranostics are drug delivery systems with molecular or targeted imaging agents integrated into their structure. The application of theranostics is rising exponentially due to the urgent need for treatments that can be utilized for diagnostic imaging as an aid in precision and personalised medicine. Subsequently, the emergence of nanobiotechnology and the green synthesis of metallic nanoparticles (MNPs) has provided one such avenue for nanoscale development and research. Of interest is the drastic rise in the use of medicinal plants in the synthesis of MNPs which have been reported to be potentially effective in the diagnosis and treatment of diseases. At present, medicinal plant-derived MNPs have been cited to have broad pharmacological applications and have been studied for their potential use in the treatment and management of cancer, malaria, microbial and cardiovascular diseases. The subject of this article regards the role of medicinal plants in the synthesis of MNPs and the potential role of MNPs in the field of theranostics.
... Furthermore, a "soft" PC may interact with the formed "hard" PC layer on the NPs' surface via weak protein-protein interaction. The "hard" PCs' protein exchange rate from the NPs' surface is slow, but this process plays an essential role in defining the NPs' activity and biological fate [87][88][89][90]. This process of adsorption of proteins on the surfaces of NPs is dynamic and it is associated with the continuous adsorption/desorption equilibrium of the proteins on and off the NP surfaces [89]. ...
... The "hard" PCs' protein exchange rate from the NPs' surface is slow, but this process plays an essential role in defining the NPs' activity and biological fate [87][88][89][90]. This process of adsorption of proteins on the surfaces of NPs is dynamic and it is associated with the continuous adsorption/desorption equilibrium of the proteins on and off the NP surfaces [89]. ...
... For this reason, a preformed protective albumin corona should limit these non-specific interactions and decrease the complement activation. In addition to reducing clearance, albumin also has structural advantages; both amino and carboxylic groups can be employed to functionalize NPs' surface by targeting ligands to facilitate transport and accumulation to the tumor site [89]. Therefore, beyond the improvement of the NPs' half-life, it is crucial to consider the NPs' distribution inside the tumor tissue. ...
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Nanoparticle-based therapies have been proposed in oncology research using various delivery methods to increase selectivity toward tumor tissues. Enhanced drug delivery through nanoparticle-based therapies could improve anti-tumor efficacy and also prevent drug resistance. However, there are still problems to overcome, such as the main biological interactions of nanocarriers. Among the various nanostructures for drug delivery, drug delivery based on polymeric nanoparticles has numerous advantages for controlling the release of biological factors, such as the ability to add a selective targeting mechanism, controlled release, protection of administered drugs, and prolonging the circulation time in the body. In addition, the functionalization of nanoparticles helps to achieve the best possible outcome. One of the most promising applications for nanoparticle-based drug delivery is in the field of onco-hematology, where there are many already approved targeted therapies, such as immunotherapies with monoclonal antibodies targeting specific tumor-associated antigens; however, several patients have experienced relapsed or refractory disease. This review describes the major nanocarriers proposed as new treatments for hematologic cancer, describing the main biological interactions of these nanocarriers and the related limitations of their use as drug delivery strategies.
... Smaller particles, furthermore, are more likely to reach intracellular regions like the mitochondria and nucleus, making them more hazardous (Kumar et al., 2017). In sum, the size of NPs is not only critical for targeting specific cellular localization, but also influences cell cytotoxicity (Lundqvist et al., 2011;Li and Lee, 2020). Furthermore, researchers have raised several safety issues that must be addressed, such as the cytotoxicity of therapeutic NPs when combined with various types of compounds, implying that the selection of nanoparticle material is critical (Jurj et al., 2017). ...
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Anti-inflammatory, antiviral, and anti-cancer treatments are potential applications of nanomaterials in biology. To explore the latest discoveries in nanotechnology, we reviewed the published literature, focusing on co-assembled nanoparticles for anti-inflammatory and anti-tumor properties, and their applications in animal husbandry. The results show that nanoparticles have significant anti-inflammation and anti-tumor effects, demonstrating broad application prospects in animal breeding. Furthermore, pooled evidence suggests that the mechanism is to have a positive impact on inflammation and tumors through the specific drug loading by indirectly or directly targeting the disease sites. Because the precise regulatory mechanism remains unclear, most studies have focused on regulating particular sites or even specific genes in the nucleus by targeting functional co-assembled nanoparticles. Hence, despite the intriguing scenarios for nanotechnology in farmed animals, most results cannot yet be translated into field applications. Overall, nanomaterials outperformed similar materials in terms of anti-inflammatory and anti-tumor. Nanotechnology also has promising applications in animal husbandry and veterinary care, and its application and development in animal husbandry remain an exciting area of research.
... Each biological microenvironment has a distinct set of proteins that interact in a specific way with the particles' surface. Protein adsorption to particles does not always require direct contact with the particle surface and may instead occur via protein-protein interactions (Li and Lee, 2020). In addition, proteins can undergo conformational changes that together with nonspecific protein-protein interactions may be interpreted as a danger-associated signal (Corbo et al., 2016); initiating an immune response that may develop into a successful defensive response or an uncalibrated inflammatory reaction (Boraschi et al., 2020). ...
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Additive manufacturing (AM) or industrial three-dimensional (3D) printing drives a new spectrum of design and production possibilities; pushing the boundaries both in the application by production of sophisticated products as well as the development of next-generation materials. AM technologies apply a diversity of feedstocks, including plastic, metallic, and ceramic particle powders with distinct size, shape, and surface chemistry. In addition, powders are often reused, which may change the particles’ physicochemical properties and by that alter their toxic potential. The AM production technology commonly relies on a laser or electron beam to selectively melt or sinter particle powders. Large energy input on feedstock powders generates several byproducts, including varying amounts of virgin microparticles, nanoparticles, spatter, and volatile chemicals that are emitted in the working environment; throughout the production and processing phases. The micro and nanoscale size may enable particles to interact with and to cross biological barriers, which could, in turn, give rise to unexpected adverse outcomes, including inflammation, oxidative stress, activation of signaling pathways, genotoxicity, and carcinogenicity. Another important aspect of AM-associated risks is emission/leakage of mono- and oligomers due to polymer breakdown and high temperature transformation of chemicals from polymeric particles, both during production, use, and in vivo, including in target cells. These chemicals are potential inducers of direct toxicity, genotoxicity, and endocrine disruption. Nevertheless, understanding whether AM particle powders and their byproducts may exert adverse effects in humans is largely lacking and urges comprehensive safety assessment across the entire AM lifecycle—spanning from virgin and reused to airborne particles. Therefore, this review will detail: 1) brief overview of the AM feedstock powders, impact of reuse on particle physicochemical properties, main exposure pathways and protective measures in AM industry, 2) role of particle biological identity and key toxicological endpoints in the particle safety assessment, and 3) next-generation toxicology approaches in nanosafety for safety assessment in AM. Altogether, the proposed testing approach will enable a deeper understanding of existing and emerging particle and chemical safety challenges and provide a strategy for the development of cutting-edge methodologies for hazard identification and risk assessment in the AM industry.
... The intravenous delivery of these NPs have a variety of challenges associated therein. One such challenge is a change in the characteristics of the original MNPs, due to the formation of protein corona [81,82]. Another challenge is the presence of phagocytic immune cells and their ability to recognize the NPs in question, which in turn can hinder their movement or induce an immune response. ...
... Properties of corona formed on NPs such as size, shape, morphology, surface charge and composition have been characterized in several studies using a variety of techniques as shown in Fig. 4. Adsorption of proteins on surfaces of NPs and associated thermodynamic parameters have been determined as well. Techniques such as gel electrophoresis and mass spectrometry have been used to elucidate the composition of corona, while other techniques have been established to detect conformational changes in these proteins [82,83]. Fig. 4(b) provides an overview of characterization methods to identify physicochemical and biological information of the NPs and the associated corona complex. ...
... For instance, Fig. 5 shows the TEM images of magnetic iron oxide nanoparticles (MIONPs) without (Fig. 5a) and with ( Fig. 5b and c) bovine serum albumin (BSA) protein corona [85]. Dynamic light scattering (DLS) is used to determine the hydrodynamic size distribution of the NPs before and after adsorption of corona [82,86]. Corona formation increases the diameter of NPs, which can be used to confirm adsorption of corona on NPs. ...
Article
Magnetic nanoparticles are widely used for in vivo applications such as in disease diagnostics-magnetic resonance imaging, treatment-magnetoresponsive therapy, hyperthermia agents and in the delivery of drugs to specific cells, due to the unique physicochemical properties which materials posses at the nanoscale. Despite important therapeutic implications of magnetic nanoparticles, a major challenge for new magnetic materials is to ensure compliance with the nano-safety regulatory framework for in vivo usage. Whilst a large number of in vitro toxicity studies have been accomplished in literature, understanding the exact fate of magnetic nanoparticles inside the human body still remains evasive. In this review, the classification and properties of magnetic nanoparticles which facilitate their in vivo applications are discussed, followed by a description of the latest toxicology advancements in the research of magnetic nanoparticles and detailed discussions on the challenges associated with the safe removal/degradation of magnetic nanoparticles inside the body. We also provide insights on how newly designed magnetic materials can be tested prior to their in vivo use and aim to provide the reader with a comprehensive understanding of the fate of magnetic nanoparticles inside human blood vessels.
... For example, Pan et al. [46] showed that smaller gold NPs (1.4 nm) induce a higher cellular toxicity compared to larger NPs (15 nm) in HeLa and L929 cells. While NPs size is a determining factor in designing nanomedicines or targeting specific subcellular localizations, their interaction with biological environments before reaching the target site may influence the way they enter cells and thus affect their toxicity [59,60]. ...
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With the advancement of nanotechnology, the nano-bio-interaction field has emerged. It is essential to enhance our understanding of nano-bio-interaction in different aspects to design nanomedicines and improve their efficacy for therapeutic and diagnostic applications. Many researchers have extensively studied the toxicological responses of cancer cells to nano-bio-interaction, while their mechanobiological responses have been less investigated. The mechanobiological properties of cells such as elasticity and adhesion play vital roles in cellular functions and cancer progression. Many studies have noticed the impacts of cellular uptake on the structural organization of cells and, in return, the mechanobiology of human cells. Mecha-nobiological changes induced by the interactions of nanomaterials and cells could alter cellular functions and influence cancer progression. Hence, in addition to biological responses, the pos-sible mechanobiological responses of treated cells should be monitored as a standard methodology to evaluate the efficiency of nanomedicines. Studying the cancer-nano-interaction in the context of cell mechanics takes our knowledge one step closer to designing safe and intelligent nanomedicines. In this review, we briefly discuss how the characteristic properties of nanoparticles influence cellular uptake. Then, we provide insight into the mechanobiological responses that may occur during the nano-bio-interactions, and finally, the important measurement techniques for the mechanobiological characterizations of cells are summarized and compared. Understanding the unknown mechanobiological responses to nano-bio-interaction will help with developing the application of nanoparticles to modulate cell mechanics for controlling cancer progression.
... In this context, CD has been used extensively to study the changes in the structures of the proteins and their folding and binding properties after forming corona on NP surfaces (Venerando et al., 2013;Fleischer and Payne, 2014;Jayaram et al., 2018;ZhangT. et al., 2019;Li and Lee, 2020;Marichal et al., 2020;Park, 2020). Impressively, Gebauer et al., (2012) investigated the protein corona formed by human serum albumin, containing α-helices as predominant secondary structural elements, around citrate-functionalized silver NP surface. ...