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Review

Hemolytic Activity of Nanoparticles as a Marker of Their Hemocompatibility

by
Saul Yedgar
1,
Gregory Barshtein
1,* and
Alexander Gural
2
1
Department of Biochemistry, The Faculty of Medicine, Hebrew University, Jerusalem 91120, Israel
2
Blood Bank, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel
*
Author to whom correspondence should be addressed.
Micromachines 2022, 13(12), 2091; https://doi.org/10.3390/mi13122091
Submission received: 29 September 2022 / Revised: 23 November 2022 / Accepted: 25 November 2022 / Published: 27 November 2022
(This article belongs to the Special Issue Nanoparticles in Biomedical Sciences)
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Abstract

:
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.

1. Introduction

Engineered man-made nanomaterials have several applications in the field of biomedicine for diagnosis [1], drug delivery [2], and therapeutics [3]. The International Organization for Standardization defines nanomaterials as structures with a size range from 1 to 100 nm in one, two, or three dimensions [4]. Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) [5,6] are the primary tools for the visualization of nanomaterial shapes (as illustrated in Figure 1). An extensive library of images of various nanomaterials has been collected [7,8,9,10,11].
Nanomaterials are drawing increasing interest from many branches of medical practices and research [6]. Their use in medical devices or as drug carriers offers opportunities for novel therapeutic approaches to treat complex disorders such as malignant, inflammatory, and neurodegenerative diseases [12,13,14].
Humans may be exposed to nanomaterials through inhalation (respiratory tract), skin contact, ingestion, or intravenous (IV) injection. The tiny size of nanomaterials allows for them to pass more easily through cell membranes [15,16]. Moreover, some nanomaterials are readily distributed throughout the body, where they are deposited in the mitochondria of the target organs and may trigger tissue injury [15]. Possible pathways for nanoparticle uptake and intracellular transport routes have been extensively discussed in the literature, and several recent reviews are hereby recommended [17,18].
Despite the advantages offered by nanotechnology, the potential risk of intended and unintended human exposure to nanomaterials is increasing as nanotechnology develops. Novel nanomaterials are currently widely used without thoroughly assessing their potential health risks. The knowledge regarding their toxic potential is still limited, without appropriate regulatory measures being implemented [4,20,21].
Early studies on asbestos and man-made nanomaterials, such as diesel exhausts, have shown that they can accumulate in the human body, especially after daily exposure, such as in occupational settings. Long-term and short-term toxicity to humans and animals caused by nanomaterials has already become a serious concern. Therefore, a new branch of science, named nanotoxicology [22,23], has emerged, aiming to study nanomaterials’ hazardous effects on human health and on the environment.
In many cases, novel nanoparticles (NPs) are widely manipulated without thoroughly assessing their potential health risks. The broad range of composition and physicochemical properties of NPs (colloidal stability, purity, inertness, size, shape, charge, etc.) make them ubiquitous and determine their interactions with other biological materials and the extent of their toxicity [24,25]. As with regular particles, the NP surface forms the point of contact with cells. Therefore, surface area and surface chemistry are essential determinants of NPs toxicity [26]. The geometry of NPs, determining their effective surface area, affects not only the interaction between NPs and plasma proteins but also the mechanism and degree of cellular absorption and, consequently, the potential toxicity of NPs [27].
Several approaches can be used to assess NP toxicity; these include epidemiological studies, human clinical studies, animal models, and in vitro models [28,29,30,31,32,33].
Whatever their use, source, and route of exposure (whether oral, respiratory, or dermal), NPs can enter the bloodstream. Several studies have reported that, due to their small size, free NPs can penetrate the alveolar lining [34,35,36], cause inflammatory reactions, and subsequently enter the bloodstream [37]. The circulation then distributes such NPs throughout the body, allowing their penetration into various organs, where they are partially metabolized, excreted, or retained. Moreover, in the bloodstream itself, the NPs interact with various blood cells [27], especially red blood cells (RBCs), the most abundant cellular component in circulation. The exposure of RBCs to NPs leads to various biochemical/biophysical and morphological changes that can significantly affect their functionality [38,39].
Under in vivo conditions (in the bloodstream), the contact between an NP and an RBC occurs in plasma, where all its components (proteins, hormones, vitamins, sugars, and inorganic ions) can affect this interaction. The effect of proteins is the most studied of all the plasma components. It is convincingly documented that the particle’s surface is covered with a corona formed by adsorbed proteins in the plasma [40]. However, most publications on this subject describe NP–RBC interaction occurring in a buffer. Accordingly, this aspect is the focus of the first section of our review. 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. A separate section discusses the various methods for assessing NP hemotoxicity. In the last section, we outline the directions for further research in this area.

2. Interaction of NPs with Red Blood Cells (RBCs) in a Protein-Free Medium

NPs (see Table 1) interact with cells differently than small molecules and are incorporated into the cell by active, energy-dependent processes. Direct NP/RBC contact can cause a change in the state of the cell membrane [44] and, in many cases, disrupts the membrane integrity leading to hemolysis. It has been previously shown that the adsorption of NPs onto the RBC surface can provoke alterations in cell morphology [45,46], the elevation of osmotic fragility [47] and rigidity [48], alterations in cells’ aggregability and adhesion to endothelial cells [49], and membrane vesiculation [50]. The consequences of the NP interaction with a cell are discussed in detail in a recent review by Tian et al. [50].
As has been summarized in several reviews [82,83], RBC hemolysis is the most extensively discussed effect of NPs. The NP hemolytic activity is considered the primary criterion for hemocompatibility [82]. Oberdörster et al. [26] proposed a list of physicochemical characteristics that might be important for understanding the biological activity and toxic properties of NPs.
In particular, the hemolytic activity of nanomaterials has been extensively studied using polystyrene nanoparticles (NPPS) [48,49,54,84]. In a previous study [49], we reported that the NPPS hemolytic activity is a function of their concentration, size, and protein concentration in the medium.
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.
Peetia and Labhasetwar [85] observed that plain NPPS induced a decrease in the cell membrane surface pressure, which was inversely proportional to the particle size, indicating a loss of phospholipids from the interface into the bulk. The authors [86] related this to the interaction of the phospholipid hydrophobic chains with hydrophobic NPs, which then mobilize the phospholipid molecules from the interface into the subphase, causing destabilization of the membrane. Moreover, the authors conclude that the modification of the particle surface leads to significant changes in the nature of its interaction with the cell membrane. It was found that double-stranded and single-stranded cationic surfactants on NPs interact differently with model membranes [86]. NPs that exhibit stronger biophysical interactions with the membrane also show greater cellular uptake.
Moreover, the authors conclude that the functionalization of the particle surface leads to significant changes in the nature of its interaction with the membrane [86]. It was found [86] that the di-chained and single-chained cationic surfactants on NPs have different interaction mechanisms with model membranes. Saha et al. [87] found that a linear hemolytic profile with increasing NP surface hydrophobicity is exhibited in the absence of plasma proteins.
The generation of oxidative stress (OS) by NPs is widely discussed in the literature [88,89,90], with convincing data suggesting that it is a common cause of damage to RBCs [91,92,93,94,95,96,97], leading to cell dysfunction [94,96,97,98] and ultimately to hemolysis [99,100]. Several studies have demonstrated the significance of reactive NPs’ surface in ROS generation [90,101]. Free radicals are generated when the oxidants and free radicals are bound to the particle surface. For example, for silica NP (NPSiO2), surface-bound radicals such as SiO• and SiO2• are responsible for the formation of ROS such as OH• and O2• [102].
Special attention was paid to evaluating the undesirable effects of gold and silver NPs (NPAu/NPAg), which are increasingly used in biomedical applications [68,69,72,74,103]. The increased interest in these nanoparticles is associated with their ability to penetrate bacterial cell membranes, change the structure of cell membranes, and even lead to cell death [104]. The effectiveness of NPAg is due to its nanosize, large surface area to volume ratio, and the ability to produce reactive oxygen species and release silver ions [105]. Finally, the generation of ROS and OS by gold and silver NPs leads to cytotoxicity and genotoxicity. [105,106]. Regarding the effect of gold and silver nanoparticles on RBCs [107,108], it was found that their incubation with cells caused significant hemolysis [109].
Interestingly, the interaction between NPAg and a red cell leads not only to a change in its membrane composition but also to an alteration in intracellular hemoglobin properties. Barkur et al. [110] studied the effect of NPAg and NPAu on RBCs using Micro-Raman Spectroscopy and observed spectral modifications, which implicate the deoxygenation of hemoglobin in NP-treated RBCs. The interaction of RBCs with NPs generally adversely affects the hemoglobin’s ability to bind oxygen, with NPAg demonstrating a relatively more substantial adverse effect than NPAu [110]. The authors hypothesized that OS triggered by NPAg caused more profound changes in the RBCs and, consequently, higher spectral variations. Barkur et al. [110] confirmed the two mechanisms involved in metal NP-induced hemoglobin deoxygenation on RBCs: the adherence of NP to the RBC membrane and OS generation. Perevedentseva et al. [61] also used Raman Spectroscopy to study the effect of NPTiO2 on the hemoglobin oxygenation state in the RBC cytoplasm. The authors postulated that the adsorption of NPTiO2 onto the cell surface leads to the partial deoxygenation of hemoglobin [61].

3. RBC as Carriers of Nanoparticles

Since RBCs are the most abundant cellular component in circulation, RBC-based drug delivery systems (DDSs) [111] have been the subject of extensive research in the last decades [112,113,114,115,116]. “Hitchhiking with RBCs” is a drug-delivery method that can increase drug concentration in target organs by orders of magnitude [117]. Accordingly, a new class of delivery systems [71,118,119,120] has been developed, consisting of human RBCs bearing NPs loaded with therapeutic agents [118]. In addition, some groups have taken a new approach to increase the circulation time of NPs by forming an RBC-NP complex, which reduces the rate of NPs’ removal from the bloodstream [121,122]. Since the attachment of NP to RBC leads to a significant change in a wide range of cell properties, a thorough study of the RBC-NP complex behavior in vitro and in vivo is necessary. In particular, it is essential to assess the sensitivity of the RBC-NP complex to oxidative, mechanical, and osmotic stresses [47,48].
Several studies have demonstrated the applicability of this approach in nanomedicine [111,123,124]. However, the effect of modified cells on the behavior of native RBCs has been little studied. In this regard, of particular interest is the work of Barshtein et al. [38], which examined the effect of RBC-NPPS on the aggregation of RBCs and their adhesion to endothelial cells (EC). Red cells were incubated with NPPS, washed, and added to a suspension of untreated RBCs at varying concentrations. The RBC-NPPS complexes induced red cell aggregates (in PBS) and markedly elevated RBC adhesion to EC. These effects were augmented by (a) increasing the concentration of RBC-NPPS and (b) decreasing the NPPS size. This implies that the RBC-NP complex can induce strong interaction with native RBCs and form large and robust aggregates with native red cells [38,39,125], as well as enhance RBC/EC interaction [58,99]. Han et al. [39] discussed the mechanism of RBC aggregation that was modulated by hydroxyapatite NPs and concluded that NP-induced RBCs aggregation could be attributed to the bridging force via the surfaces of NPs and RBCs. The authors consider two alternative RBC aggregation models proposed to describe RBCs aggregation in a medium containing macromolecule and suggest the bridging model [126,127] as a preferred one.

4. Corona Formation

In the blood, a layer of plasma components is adsorbed onto the NP surface, modifies its properties, and imparts it with a new identity [128,129]. Therefore, under physiological conditions, RBCs do not directly interact with the NP surface, but rather with plasma proteins bound to the particle with varying strengths [130,131,132], named “corona” [129,133,134,135]. For a single-protein solution, it has been shown that the protein binds to the NP with micromolar affinity, depending on surface properties [134,136,137]. However, when NP is suspended in plasma (which contains numerous types of proteins), proteins that first adsorb to its surface are later replaced by others (Vroman effect, [138]) with a higher affinity for the surface [138,139,140]. The exchange mechanisms are still being explored [139,141,142]. The character of the surface has been shown to affect the affinity [143,144] and the eventual balance between the adsorbed proteins [145,146]. Moreover, the stability of the protein layer on the NP can affect the NP-RBC interaction (adhesion [147], hemolytic activity [49]), and cellular uptake [148]).
In addition, the protein corona composition is sensitive to the NP surface functionalization. For example, Kelpsiene et al. [149] found that aminated NPPS bind a different set of proteins than carboxylated NPPS.
Notably, modern approaches that use artificial intelligence are now being implemented to predict corona composition and help explain the biological compatibility of NPs [150,151,152,153]. Moreover, the method reported by Bun and colleagues [150] successfully predicted cellular recognition (e.g., cellular uptake by macrophages and cytokine release) and nanotoxicity mediated by functional corona proteins.
As we demonstrated, forming a corona around nanomaterials is a complex process, and, for a comprehensive introduction to this topic, we recommend several reviews [128,129,130,131,132] selected from a long list of relevant publications.

5. RBC Interaction with Corona-Coated NP

The NP adhesion to the cell surface is critical in determining their interaction level. The inhibition of NP/RBC adhesion may be induced by covering the surface with corona proteins [148,154]. The corona can be created intentionally (by pretreatment of particles) or spontaneously (following the interaction of NP with plasma proteins). As noted above, in the plasma or other body fluids, the NP/RBC interaction is not with the NP itself but with the particle’s corona proteins. The biophysical explanation for the relationship between protein adsorption onto NP surfaces and the NP interaction with red cells is complicated, as many factors, such as the NP and RBC properties and the environment around them, influence this.
In a previous publication [49], we suggested that the protein coating of NPs should decrease their hemolytic activity. To test this hypothesis, we determined the hemolytic activity of uncoated and albumin-treated NPPS (as albumin is an inhibitor of NP/RBC interaction [147]). It was found that at a concentration of 0.05% albumin, the NPPs’ hemolytic capacity is totally inhibited, despite the fact that, at this concentration, only 30–50% of the NP surface is covered with protein [134,155]. Thus, we concluded that the formation of an albumin corona on NPPs leads to a sharp decrease in their hemolytic activity.
Similarly, Yeo et al. [156] found that gold nanorods treated with a serum to form a protein corona on their surface exhibited hemolytic activity of less than 0.2%, with no observable effect on RBC morphology.
Saha et al. [87] considered a more complex issue. They synthesized a class of cationic NPAu with the same core size (~2 nm) but different surface functionalities induced by changing the surface hydrophobicity and determined their hemolytic activity in the presence and absence of plasma proteins. They found a critical synergy between the chemical functions of the NP surface and the protein corona, with corona formation leading to a sharp decrease in the NP hemolytic activity. The presence of plasma proteins prevented the hemolytic activity of both hydrophilic and hydrophobic NPs [87].

6. Methods for Assessment of Nanomaterials’ Hemotoxicity

Nano-toxicology is a fast-developing area of nanoscience and nanotechnology. Current studies on the toxic effects of NPs, aiming to identifying the mechanisms of their harmful effects, are carried out in cell culture and animal models [54,55,57,59,157,158,159,160,161,162].
The toxicity of NPPS has received special attention [162,163,164,165]. These particles can be easily synthesized in a wide range of sizes, and their surfaces can be given different functionality [59]. Thus, they are ideally suited as a model for studying the effect of particle surface characteristics on various biological parameters both in vitro and in vivo. Sarma and colleagues [54] have analyzed the cytotoxic and genotoxic potential of NPPS on human peripheral lymphocytes (in vitro), while Loos et al. [59] have summarized information regarding the effect of functionalized (positively and negatively charged) NPPS on macrophages and THP-1 cells (in vitro). These studies indicate that while polystyrene is non-toxic, functionalized nanoparticles may behave differently than bulk material, and surface chemistry plays a critical role in determining the effect of NPPS on various cells.
The toxicity of NPPS was also analyzed in vivo in animal models [159,160,161,162]. Fan et al. [160] observed the accumulation of fluorescent NPPS in various organs of mice after oral ingestion, including in the liver, kidney, spleen, and pancreas. The main mechanism of damage to the internal organs was the impairment of liver function and lipid metabolism. Yasin and colleagues also identified the striking hepatoxicity of NPPS (in a dose-dependent manner) [162] in rats. In addition, a recent in vivo study showed that PSNPs induced reproductive toxicity [161] in mice, caused fetal growth restriction, and significantly impaired cholesterol metabolism in both the mice’s placenta and the fetus [159].
However, the toxicity and risk associated with the use of NPs still need to be understood in their entirety [95]. The development of an adequate experimental strategy for estimating NPs’ toxicity should include the choice between in vitro (cell lines) and in vivo (animal models) methods or a combination of both, as both methods have advantages and disadvantages. The NP toxic effects on individual cell components and tissues are more accessible for in vitro analysis, while in vivo models enable the assessment of NP toxicity for individual organs or the whole organism [163]. It seems more logical to first test NP toxicity on cells, and if toxic effects are clearly demonstrated, this may spare the need for animal testing, in accordance with the global trend of reducing the number of animal experiments [97,98].
The rapid growth of nanomedicine and the development of more and more new NPs make in vivo toxicity tests undesirable on both ethical and financial grounds, creating an urgent need to develop in vitro cell-based assays that accurately predict in vivo toxicity and facilitate safe nanotechnology.
Of all the cell types [164] that can be used to assess the toxicity of nanomaterials, the choice of RBC as a target cell seems to be the most useful. As noted above, irrespective of their use, source, and route of exposure, NPs enter the bloodstream and interact with RBCs, the major cellular component in the circulation (4–5 million RBCs per 1 μL of blood), producing a negative effect on their functionality. As RBCs are well characterized, accessible, and easy to manipulate, they make an excellent candidate for being the target cells for nanotoxicity assessment.
Numerous studies have examined the NP-RBC interaction, focusing on the hemolytic potential of NPs [49,165], suggesting that this is the critical test of NP safety [75,166]. Although hemolysis tests have been conducted with various NPs, comparing results across studies is difficult due to the variability of protocols implemented for particle characterization and hemolysis testing [52].
The American Society for Testing and Materials (ASTM) published (2008) a standard test protocol for the assessment of NPs’ hemolytic properties [166], which determines the percentage of hemoglobin (Hb) released after NP-RBC interaction. The hemolytic assay has proven to be a promising test for surveying nanomaterial toxicity [167] due to its low cost, good reproducibility, and quick results [77]. To date, hemolytic activity has even been demonstrated with therapeutic NPs in vitro [73,168,169] and in vivo [170,171], indicating the potential adverse effects of NPs, which may limit their applications in nanomedicine.
Cho et al. [172] studied the nanotoxicity of a panel of NPs (CeO2, TiO2, carbon black, SiO2, NiO, Co3O4, Cr2O3, CuO, and ZnO). The authors compared the acute lung inflammogenicity in a rat model with in vitro toxicity. For in vitro testing, eight different cell-based assays were used, including epithelial cells, monocytic/macrophage cells, human erythrocytes, and combined culture. Cytotoxicity in differentiated peripheral blood mononuclear cells was the most accurate, demonstrating 89% accuracy and 11% false negative results in predicting acute pulmonary inflammation. However, only hemolysis tests demonstrated a 100% match with lung inflammation at all NP concentrations. Other in vitro cellular assays showed a weaker correlation with in vivo inflammatory activity.
An analysis of the related literature supports the finding that NP-induced hemolytic activity can assess in vivo NP toxicity and has been proposed as a critical test in determining NP hemocompatibility [75,77,166,173]. However, despite the attempts to develop a unified protocol to determine NPs’ hemolytic activity, the measurement conditions used by various research groups still differ significantly [52].
For a universal protocol, it is necessary to consider that forming a protein corona around NP inhibits its effective hemolytic activity. In addition, the interaction between a red cell and a nanoparticle in the bloodstream occurs under flow-induced mechanical stress, which can cause RBC deformation [174] and stimulate NP hemolytic activity [47]. Thus, it would be appropriate to test NP hemocompatibility under mechanical stress conditions in a medium supplemented by plasma proteins or in the plasma itself (and not in a buffer, as is customary in many laboratories).
The ability of an NP to change RBC properties can be expressed as an alteration in its functionality and, in its extreme form, as the destruction of the cell [38,175,176]. Therefore, other properties of red cells, such as their aggregability, deformability, and adhesion to EC, should be considered alternative markers to NP hemolytic activity [38,175,176].
All of the mentioned studies demonstrate the protective role of the protein corona formed on the nanomaterial’s surface, improving the NP hemocompatibility and providing promising options for the design of therapeutic nanomaterials without prohibitive toxic effects.
Thus, we can summarize that the NPs’ characteristics and the plasma composition are the dominant factors determining the NPs’ hemocompatibility. Additional factors that can affect the NP hemolytic ability inclue the properties of the RBCs themselves and the presence of mechanical stress (Figure 2). For these reasons, when developing a protocol for testing the hemolytic activity of NPs, it is necessary to consider all four factors.

7. Conclusions

The application of nanotechnology to medicine is expected to have a revolutionary impact on health care [115,116,117] and has already stimulated the emergence of relatively new areas, such as nanotoxicology. It is evident that, with the expansion of NP use, the need to assess the toxicity of new materials also grows. However, assessing NP toxicity is a costly process that includes several steps. As discussed above and further detailed in additional publications [70,177,178], an in vitro assay is a superior method for preliminary toxicity assessments. While, at present, the tests for NPs’ hemolytic activity are the most widely adopted, they ignore several important factors, particularly the need to assess hemolysis in the presence of plasma proteins and under conditions of mechanical stress. Furthermore, when considering the use of NPs for treating pathologies related to impaired RBC function (e.g., diabetes, hemoglobinopathies, and others), toxicity testing should be carried out using cells specific to these conditions.
Finally, we hope this review will promote further research on NP-RBC interactions and encourage researchers to develop simple and effective in vitro tests to assess NP hemocompatibility.

Author Contributions

Conceptualization, S.Y.; writing—original draft preparation, G.B.; writing—review and editing, S.Y. and A.G.; supervision, S.Y. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Ding, H.; Zhang, J.; Zhang, F.; Xu, Y.; Liang, W.; Yu, Y. Nanotechnological approaches for diagnosis and treatment of ovarian cancer: A review of recent trends. Drug Deliv. 2022, 29, 3218–3232. [Google Scholar] [CrossRef] [PubMed]
  2. Parhiz, H.; Khoshnejad, M.; Myerson, J.W.; Hood, E.; Patel, P.N.; Brenner, J.S.; Muzykantov, V.R. Unintended effects of drug carriers: Big issues of small particles. Adv. Drug Deliv. Rev. 2018, 130, 90–112. [Google Scholar] [CrossRef] [PubMed]
  3. Ding, Y.N.; Xue, M.; Tang, Q.S.; Wang, L.J.; Ding, H.Y.; Li, H.; Gao, C.C.; Yu, W.P. Immunotherapy-based novel nanoparticles in the treatment of gastrointestinal cancer: Trends and challenges. World J. Gastroenterol. 2022, 28, 5403–5419. [Google Scholar] [CrossRef] [PubMed]
  4. Buzea, C.; Pacheco, I.I.; Robbie, K. Nanomaterials and nanoparticles: Sources and toxicity. Biointerphases 2007, 2, MR17–MR71. [Google Scholar] [CrossRef] [Green Version]
  5. Malatesta, M. Transmission Electron Microscopy as a Powerful Tool to Investigate the Interaction of Nanoparticles with Subcellular Structures. Int. J. Mol. Sci. 2021, 22, 12789. [Google Scholar] [CrossRef]
  6. Yohan, D.; Chithrani, B.D. Applications of nanoparticles in nanomedicine. J. Biomed. Nanotechnol. 2014, 10, 2371–2392. [Google Scholar] [CrossRef]
  7. Chen, F.; Hong, H.; Shi, S.; Goel, S.; Valdovinos, H.F.; Hernandez, R.; Theuer, C.P.; Barnhart, T.E.; Cai, W. Engineering of Hollow Mesoporous Silica Nanoparticles for Remarkably Enhanced Tumor Active Targeting Efficacy. Sci. Rep. 2014, 4, 5080. [Google Scholar] [CrossRef] [Green Version]
  8. Gohari, G.; Mohammadi, A.; Akbari, A.; Panahirad, S.; Dadpour, M.R.; Fotopoulos, V.; Kimura, S. Titanium dioxide nanoparticles (TiO2 NPs) promote growth and ameliorate salinity stress effects on essential oil profile and biochemical attributes of Dracocephalum moldavica. Sci. Rep. 2020, 10, 912. [Google Scholar] [CrossRef] [Green Version]
  9. Jiang, Y.; Zheng, W.; Tran, K.; Kamilar, E.; Bariwal, J.; Ma, H.; Liang, H. Hydrophilic nanoparticles that kill bacteria while sparing mammalian cells reveal the antibiotic role of nanostructures. Nat. Commun. 2022, 13, 197. [Google Scholar] [CrossRef]
  10. Loiseau, A.; Asila, V.; Boitel-Aullen, G.; Lam, M.; Salmain, M.; Boujday, S. Silver-Based Plasmonic Nanoparticles for and Their Use in Biosensing. Biosensors 2019, 9, 78. [Google Scholar] [CrossRef]
  11. Meen, T.-H.; Tsai, J.-K.; Chao, S.-M.; Lin, Y.-C.; Wu, T.-C.; Chang, T.-Y.; Ji, L.-W.; Water, W.; Chen, W.-R.; Tang, I.-T.; et al. Surface plasma resonant effect of gold nanoparticles on the photoelectrodes of dye-sensitized solar cells. Nanoscale Res. Lett. 2013, 8, 450. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  12. Kher, C.; Kumar, S. The Application of Nanotechnology and Nanomaterials in Cancer Diagnosis and Treatment: A Review. Cureus 2022, 14, e29059. [Google Scholar] [CrossRef] [PubMed]
  13. Moradpoor, H.; Safaei, M.; Mozaffari, H.R.; Sharifi, R.; Imani, M.M.; Golshah, A.; Bashardoust, N. An overview of recent progress in dental applications of zinc oxide nanoparticles. RSC Adv. 2021, 11, 21189–21206. [Google Scholar] [CrossRef]
  14. Murthy, S.K. Nanoparticles in modern medicine: State of the art and future challenges. Int. J. Nanomed. 2007, 2, 129–141. [Google Scholar]
  15. Nel, A.; Xia, T.; Madler, L.; Li, N. Toxic Potential of Materials at the Nanolevel. Science 2006, 311, 622–627. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  16. Xia, T.; Kovochich, M.; Liong, M.; Mädler, L.; Gilbert, B.; Shi, H.; Yeh, J.I.; Zink, J.I.; Nel, A.E. Comparison of the Mechanism of Toxicity of Zinc Oxide and Cerium Oxide Nanoparticles Based on Dissolution and Oxidative Stress Properties. ACS Nano 2008, 2, 2121–2134. [Google Scholar] [CrossRef] [Green Version]
  17. Donahue, N.D.; Acar, H.; Wilhelm, S. Concepts of nanoparticle cellular uptake, intracellular trafficking, and kinetics in nanomedicine. Adv. Drug Deliv. Rev. 2019, 143, 68–96. [Google Scholar] [CrossRef]
  18. Foroozandeh, P.; Aziz, A.A. Insight into Cellular Uptake and Intracellular Trafficking of Nanoparticles. Nanoscale Res. Lett. 2018, 13, 339. [Google Scholar] [CrossRef] [Green Version]
  19. Petithory, T.; Pieuchot, L.; Josien, L.; Ponche, A.; Anselme, K.; Vonna, L. Size-Dependent Internalization Efficiency of Macrophages from Adsorbed Nanoparticle-Based Monolayers. Nanomaterials 2021, 11, 1963. [Google Scholar] [CrossRef]
  20. De La Cruz, G.G.; Rodríguez-Fragoso, P.; Reyes-Esparza, J.; Rodríguez-López, A.; Gómez-Cansino, R.; Rodriguez-Fragoso, L. Interaction of Nanoparticles with Blood Components and Associated Pathophysiological Effects. In Unraveling the Safety Profile of Nanoscale Particles and Materials; de Casto Gomez, A.F.S.M., Ed.; IntechOpen: London, UK, 2018; pp. 168–180. [Google Scholar]
  21. Fard, J.K.; Jafari, S.; Eghbal, M.A. A Review of Molecular Mechanisms Involved in Toxicity of Nanoparticles. Adv. Pharm. Bull. 2015, 5, 447–454. [Google Scholar] [CrossRef]
  22. Greish, K.; Thiagarajan, G.; Ghandehari, H. In Vivo Methods of Nanotoxicology. Methods Mol. Biol. 2012, 926, 235–253. [Google Scholar] [CrossRef] [PubMed]
  23. Santamaria, A. Historical Overview of Nanotechnology and Nanotoxicology. Methods Mol. Biol. 2012, 926, 1–12. [Google Scholar] [CrossRef] [PubMed]
  24. Luyts, K.; Napierska, D.; Nemery, B.; Hoet, P.H.M. How physico-chemical characteristics of nanoparticles cause their toxicity: Complex and unresolved interrelations. Environ. Sci. Process. Impacts 2013, 15, 23–38. [Google Scholar] [CrossRef]
  25. Wu, Y.-L.; Putcha, N.; Ng, K.W.; Leong, D.T.; Lim, C.T.; Loo, S.C.J.; Chen, X. Biophysical Responses upon the Interaction of Nanomaterials with Cellular Interfaces. Accounts Chem. Res. 2012, 46, 782–791. [Google Scholar] [CrossRef] [PubMed]
  26. Oberdörster, G.; Maynard, A.; Donaldson, K.; Castranova, V.; Fitzpatrick, J.; Ausman, K.; Carter, J.; Karn, B.; Kreyling, W.; Lai, D.; et al. Principles for characterizing the potential human health effects from exposure to nanomaterials: Elements of a screening strategy. Part. Fibre Toxicol. 2005, 2, 8. [Google Scholar] [CrossRef] [PubMed]
  27. de la Harpe, K.M.; Kondiah, P.P.; Choonara, Y.E.; Marimuthu, T.; du Toit, L.C.; Pillay, V. The Hemocompatibility of Nanoparticles: A Review of Cell–Nanoparticle Interactions and Hemostasis. Cells 2019, 8, 1209. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  28. Stone, V.; Johnston, H.; Schins, R.P.F. Development of in vitro systems for nanotoxicology: Methodological considerations. Crit. Rev. Toxicol. 2009, 39, 613–626. [Google Scholar] [CrossRef]
  29. Savage, D.T.; Hilt, J.Z.; Dziubla, T.D. In Vitro Methods for Assessing Nanoparticle Toxicity. Methods Mol. Biol. 2019, 1894, 1–29. [Google Scholar] [CrossRef]
  30. Odeyemi, S.W.; De La Mare, J.; Edkins, A.L.; Afolayan, A.J. In vitro and in vivo toxicity assessment of biologically synthesized silver nanoparticles from Elaeodendron croceum. J. Complement. Integr. Med. 2019, 16. [Google Scholar] [CrossRef]
  31. Pardeshi, S.R.; More, M.P.; Patil, P.B.; Mujumdar, A.; Naik, J.B. Statistical optimization of voriconazole nanoparticles loaded carboxymethyl chitosan-poloxamer based in situ gel for ocular delivery: In vitro, ex vivo, and toxicity assessment. Drug Deliv. Transl. Res. 2022, 12, 3063–3082. [Google Scholar] [CrossRef]
  32. Yazhiniprabha, M.; Vaseeharan, B. In vitro and in vivo toxicity assessment of selenium nanoparticles with significant larvicidal and bacteriostatic properties. Mater. Sci. Eng. C Mater. Biol. Appl. 2019, 103, 109763. [Google Scholar] [CrossRef]
  33. Yazhiniprabha, M.; Vaseeharan, B.; Sonawane, A.; Behera, A. In vitro and In vivo toxicity assessment of phytofabricated ZnO nanoparticles showing bacteriostatic effect and larvicidal efficacy against Culex quinquefasciatus. J. Photochem. Photobiol. B Biol. 2019, 192, 158–169. [Google Scholar] [CrossRef] [PubMed]
  34. Basith, S.; Manavalan, B.; Shin, T.H.; Park, C.B.; Lee, W.-S.; Kim, J.; Lee, G. The Impact of Fine Particulate Matter 2.5 on the Cardiovascular System: A Review of the Invisible Killer. Nanomaterials 2022, 12, 2656. [Google Scholar] [CrossRef] [PubMed]
  35. Nemmar, A.; Hoet, P.; Vanquickenborne, B.; Dinsdale, D.; Thomeer, M.; Hoylaerts, M.; Vanbilloen, H.; Mortelmans, L.; Nemery, B. Passage of Inhaled Particles Into the Blood Circulation in Humans. Circulation 2002, 105, 411–414. [Google Scholar] [CrossRef] [Green Version]
  36. Nemmar, A.; Vanbilloen, H.; Hoylaerts, M.F.; Hoet, P.H.M.; Verbruggen, A.; Nemery, B. Passage of Intratracheally Instilled Ultrafine Particles from the Lung into the Systemic Circulation in Hamster. Am. J. Respir. Crit. Care Med. 2001, 164, 1665–1668. [Google Scholar] [CrossRef]
  37. Blank, F.; von Garnier, C.; Gehr, P.; Rothen-Rutishauser, B. Translocation across the Air–Blood Tissue Barrier. In Nanoparticles in the Lung, 1st ed.; Tsuda, A., Gehr, P., Eds.; CRC Press: Boca Raton, FL, USA, 2015. [Google Scholar]
  38. Barshtein, G.; Livshits, L.; Shvartsman, L.D.; Shlomai, N.O.; Yedgar, S.; Arbell, D. Polystyrene Nanoparticles Activate Erythrocyte Aggregation and Adhesion to Endothelial Cells. Cell Biophys. 2015, 74, 19–27. [Google Scholar] [CrossRef] [PubMed]
  39. Han, Y.; Wang, X.; Dai, H.; Li, S. Nanosize and Surface Charge Effects of Hydroxyapatite Nanoparticles on Red Blood Cell Suspensions. ACS Appl. Mater. Interfaces 2012, 4, 4616–4622. [Google Scholar] [CrossRef]
  40. Guo, S.; Shi, Y.; Liang, Y.; Liu, L.; Sun, K.; Li, Y. Relationship and improvement strategies between drug nanocarrier characteristics and hemocompatibility: What can we learn from the literature. Asian J. Pharm. Sci. 2021, 16, 551–576. [Google Scholar] [CrossRef] [PubMed]
  41. Ahsan, S.M.; Rao, C.M.; Ahmad, M.F. Nanoparticle-Protein Interaction: The Significance and Role of Protein Corona. Adv. Exp. Med. Biol. 2018, 1048, 175–198. [Google Scholar] [CrossRef]
  42. Li, Y.; Lee, J.-S. Insights into Characterization Methods and Biomedical Applications of Nanoparticle–Protein Corona. Materials 2020, 13, 3093. [Google Scholar] [CrossRef]
  43. Park, S.J. Protein–Nanoparticle Interaction: Corona Formation and Conformational Changes in Proteins on Nanoparticles. Int. J. Nanomed. 2020, 15, 5783–5802. [Google Scholar] [CrossRef]
  44. Zhang, X.; Zhang, Y.; Zheng, Y.; Wang, B. Mechanical characteristics of human red blood cell membrane change due to C60 nanoparticle infiltration. Phys. Chem. Chem. Phys. 2012, 15, 2473–2481. [Google Scholar] [CrossRef] [PubMed]
  45. Kozelskaya, A.; Panin, A.; Khlusov, I.; Mokrushnikov, P.; Zaitsev, B.; Kuzmenko, D.; Vasyukov, G.Y. Morphological changes of the red blood cells treated with metal oxide nanoparticles. Toxicol. In Vitro 2016, 37, 34–40. [Google Scholar] [CrossRef] [PubMed]
  46. Tsui, S.M.; Ahmed, R.; Amjad, N.; Ahmed, I.; Yang, J.; Manno, F.A.M.; Barman, I.; Shih, W.-C.; Lau, C. Single red blood cell analysis reveals elevated hemoglobin in poikilocytes. J. Biomed. Opt. 2020, 25, 015004. [Google Scholar] [CrossRef]
  47. Pan, D.; Vargas-Morales, O.; Zern, B.; Anselmo, A.C.; Gupta, V.; Zakrewsky, M.; Mitragotri, S.; Muzykantov, V. The Effect of Polymeric Nanoparticles on Biocompatibility of Carrier Red Blood Cells. PLoS ONE 2016, 11, e0152074. [Google Scholar] [CrossRef] [Green Version]
  48. Pan, D.C.; Myerson, J.W.; Brenner, J.S.; Patel, P.N.; Anselmo, A.; Mitragotri, S.; Muzykantov, V. Nanoparticle Properties Modulate Their Attachment and Effect on Carrier Red Blood Cells. Sci. Rep. 2018, 8, 1615. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  49. Barshtein, G.; Arbell, D.; Yedgar, S. Hemolytic Effect of Polymeric Nanoparticles: Role of Albumin. IEEE Trans. NanoBiosci. 2011, 10, 259–261. [Google Scholar] [CrossRef]
  50. Tian, Y.; Tian, Z.; Dong, Y.; Wang, X.; Zhan, L. Current advances in nanomaterials affecting morphology, structure, and function of erythrocytes. RSC Adv. 2021, 11, 6958–6971. [Google Scholar] [CrossRef]
  51. Barbul, A.; Singh, K.; Horev−Azaria, L.; Dasgupta, S.; Auth, T.; Korenstein, R.; Gompper, G. Nanoparticle-Decorated Erythrocytes Reveal That Particle Size Controls the Extent of Adsorption, Cell Shape, and Cell Deformability. ACS Appl. Nano Mater. 2018, 1, 3785–3799. [Google Scholar] [CrossRef]
  52. Dobrovolskaia, M.A.; McNeil, S.E. Understanding the correlation between in vitro and in vivo immunotoxicity tests for nanomedicines. J. Control. Release 2013, 172, 456–466. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  53. Qiao, R.; Mortimer, M.; Richter, J.; Rani-Borges, B.; Yu, Z.; Heinlaan, M.; Lin, S.; Ivask, A. Hazard of polystyrene micro-and nanospheres to selected aquatic and terrestrial organisms. Sci. Total Environ. 2022, 853, 158560. [Google Scholar] [CrossRef]
  54. Sarma, D.K.; Dubey, R.; Samarth, R.M.; Shubham, S.; Chowdhury, P.; Kumawat, M.; Verma, V.; Tiwari, R.R.; Kumar, M. The Biological Effects of Polystyrene Nanoplastics on Human Peripheral Blood Lymphocytes. Nanomaterials 2022, 12, 1632. [Google Scholar] [CrossRef] [PubMed]
  55. Shimizu, Y.; Isoda, K.; Tezuka, E.; Yufu, T.; Nagai, Y.; Ishida, I.; Tezuka, M. Influence of 50-nm polystyrene particles in inducing cytotoxicity in mice co-injected with carbon tetrachloride, cisplatin, or paraquat. Die Pharm. 2012, 67, 712–714. [Google Scholar]
  56. Anguissola, S.; Garry, D.; Salvati, A.; O’Brien, P.J.; Dawson, K.A. High Content Analysis Provides Mechanistic Insights on the Pathways of Toxicity Induced by Amine-Modified Polystyrene Nanoparticles. PLoS ONE 2014, 9, e108025. [Google Scholar] [CrossRef] [PubMed]
  57. Canesi, L.; Ciacci, C.; Bergami, E.; Monopoli, M.; Dawson, K.; Papa, S.; Canonico, B.; Corsi, I. Evidence for immunomodulation and apoptotic processes induced by cationic polystyrene nanoparticles in the hemocytes of the marine bivalve Mytilus. Mar. Environ. Res. 2015, 111, 34–40. [Google Scholar] [CrossRef] [PubMed]
  58. Kim, E.-H.; Choi, S.; Kim, D.; Park, H.J.; Bian, Y.; Choi, S.H.; Chung, H.Y.; Bae, O.-N. Amine-modified nanoplastics promote the procoagulant activation of isolated human red blood cells and thrombus formation in rats. Part. Fibre Toxicol. 2022, 19, 60. [Google Scholar] [CrossRef]
  59. Loos, C.; Syrovets, T.; Musyanovych, A.; Mailänder, V.; Landfester, K.; Nienhaus, G.U.; Simmet, T. Functionalized polystyrene nanoparticles as a platform for studying bio–nano interactions. Beilstein J. Nanotechnol. 2014, 5, 2403–2412. [Google Scholar] [CrossRef] [Green Version]
  60. Bian, Y.; Chung, H.-Y.; Bae, O.-N.; Lim, K.-M.; Chung, J.-H.; Pi, J. Titanium dioxide nanoparticles enhance thrombosis through triggering the phosphatidylserine exposure and procoagulant activation of red blood cells. Part. Fibre Toxicol. 2021, 18, 28. [Google Scholar] [CrossRef]
  61. Perevedentseva, E.; Lin, Y.-C.; Karmenyan, A.; Wu, K.-T.; Lugovtsov, A.; Shirshin, E.; Priezzhev, A.; Cheng, C.-L. Raman Spectroscopic Study of TiO2 Nanoparticles’ Effects on the Hemoglobin State in Individual Red Blood Cells. Materials 2021, 14, 5920. [Google Scholar] [CrossRef]
  62. Unnithan, J.; Rehman, M.U.; Ahmad, F.J.; Samim, M. Concentration dependent toxicity of approximately 20 nm anatase titanium dioxide nanoparticles--an in vivo study on Wistar rats. J. Biomed. Nanotechnol. 2011, 7, 207–208. [Google Scholar] [CrossRef]
  63. Karageorgou, M.-A.; Bouziotis, P.; Vranješ-Djurić, S.; Stamopoulos, D. Hemocompatibility of gallium-68 labeled iron oxide nanoparticles coated with 2,3-dicarboxypropane-1,1-diphosphonic acid. Mater. Sci. Eng. C 2020, 115, 111121. [Google Scholar] [CrossRef] [PubMed]
  64. Wang, X.; Li, P.; Jing, X.; Zhou, Y.; Shao, Y.; Zheng, M.; Wang, J.; Ran, H.; Tang, H. Folate-modified erythrocyte membrane nanoparticles loaded with Fe3O4 and artemisinin enhance ferroptosis of tumors by low-intensity focused ultrasound. Front. Oncol. 2022, 12, 864444. [Google Scholar] [CrossRef] [PubMed]
  65. Yang, S.; Lin, Y.; Zhang, L.; Sun, L.; Li, J. The in vivo investigation of Fe3O4-nanoparticles acute toxicity in mice. Biomed. Eng. Appl. Basis Commun. 2012, 224, 229–234. [Google Scholar]
  66. Mohammed, R.S.; Aadim, K.A.; Ahmed, K.A. Estimation of in vivo toxicity of MgO/ZnO core/shell nanoparticles synthesized by eco-friendly non-thermal plasma technology. Appl. Nanosci. 2022, 1–13. [Google Scholar] [CrossRef]
  67. Shaikh, S.; Shyama, S.; Desai, P. Absorption, LD50 and Effects of CoO, MgO and PbO Nanoparticles on Mice “Mus musculus”. J. Environ. Sci. Toxicol. Food Technol. 2015, 9, 32–38. [Google Scholar]
  68. Chen, Y.; Feng, X. Gold nanoparticles for skin drug delivery. Int. J. Pharm. 2022, 625, 122122. [Google Scholar] [CrossRef]
  69. Chen, Y.-S.; Hung, Y.-C.; Liau, I.; Huang, G.S. Assessment of the In Vivo Toxicity of Gold Nanoparticles. Nanoscale Res. Lett. 2009, 4, 858–864. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  70. Hou, S.; Hasnat, M.; Chen, Z.; Liu, Y.; Baig, M.M.F.A.; Liu, F.; Chen, Z. Application Perspectives of Nanomedicine in Cancer Treatment. Front. Pharmacol. 2022, 13, 909526. [Google Scholar] [CrossRef]
  71. Mac, J.T.; Nuñez, V.; Burns, J.M.; Guerrero, Y.A.; Vullev, V.I.; Anvari, B. Erythrocyte-derived nano-probes functionalized with antibodies for targeted near infrared fluorescence imaging of cancer cells. Biomed. Opt. Express 2016, 7, 1311–1322. [Google Scholar] [CrossRef] [Green Version]
  72. Burdușel, A.-C.; Gherasim, O.; Grumezescu, A.M.; Mogoantă, L.; Ficai, A.; Andronescu, E. Biomedical Applications of Silver Nanoparticles: An Up-to-Date Overview. Nanomaterials 2018, 8, 681. [Google Scholar] [CrossRef] [Green Version]
  73. Choi, J.; Reipa, V.; Hitchins, V.M.; Goering, P.L.; Malinauskas, R.A. Physicochemical Characterization and In Vitro Hemolysis Evaluation of Silver Nanoparticles. Toxicol. Sci. 2011, 123, 133–143. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  74. Nicolae-Maranciuc, A.; Chicea, D.; Chicea, L.M. Ag Nanoparticles for Biomedical Applications—Synthesis and Characterization—A Review. Int. J. Mol. Sci. 2022, 23, 5778. [Google Scholar] [CrossRef] [PubMed]
  75. Ferenc, M.; Katir, N.; Miłowska, K.; Bousmina, M.; Majoral, J.-P.; Bryszewska, M.; El Kadib, A. Haemolytic activity and cellular toxicity of SBA-15-type silicas: Elucidating the role of the mesostructure, surface functionality and linker length. J. Mater. Chem. B 2015, 3, 2714–2724. [Google Scholar] [CrossRef] [PubMed]
  76. Liu, T.; Li, L.; Teng, X.; Huang, X.; Liu, H.; Chen, D.; Ren, J.; He, J.; Tang, F. Single and repeated dose toxicity of mesoporous hollow silica nanoparticles in intravenously exposed mice. Biomaterials 2011, 32, 1657–1668. [Google Scholar] [CrossRef] [PubMed]
  77. Martinez, D.S.T.; Paula, A.J.; Fonseca, L.C.; Luna, L.A.V.; Silveira, C.P.; Durán, N.; Alves, O.L. Monitoring the Hemolytic Effect of Mesoporous Silica Nanoparticles after Human Blood Protein Corona Formation. Eur. J. Inorg. Chem. 2015, 2015, 4595–4602. [Google Scholar] [CrossRef]
  78. Abdelghafar, A.; Yousef, N.; Askoura, M. Zinc oxide nanoparticles reduce biofilm formation, synergize antibiotics action and attenuate Staphylococcus aureus virulence in host; an important message to clinicians. BMC Microbiol. 2022, 22, 244. [Google Scholar] [CrossRef]
  79. Pasupuleti, S.; Alapati, S.; Ganapathy, S.; Anumolu, G.; Pully, N.R.; Prakhya, B.M. Toxicity of zinc oxide nanoparticles through oral route. Toxicol. Ind. Health 2011, 28, 675–686. [Google Scholar] [CrossRef] [PubMed]
  80. Babu, E.P.; Subastri, A.; Suyavaran, A.; Premkumar, K.; Sujatha, V.; Aristatile, B.; Alshammari, G.M.; Dharuman, V.; Thirunavukkarasu, C. Size Dependent Uptake and Hemolytic Effect of Zinc Oxide Nanoparticles on Erythrocytes and Biomedical Potential of ZnO-Ferulic acid Conjugates. Sci. Rep. 2017, 7, 4203. [Google Scholar] [CrossRef] [Green Version]
  81. Rajkumar, K.; Mvs, S.; Koganti, S.; Burgula, S. Selenium Nanoparticles Synthesized Using Pseudomonas stutzeri (MH191156) Show Antiproliferative and Anti-angiogenic Activity Against Cervical Cancer Cells. Int. J. Nanomed. 2020, 15, 4523–4540. [Google Scholar] [CrossRef]
  82. Fröhlich, E. Hemocompatibility of inhaled environmental nanoparticles: Potential use of in vitro testing. J. Hazard. Mater. 2017, 336, 158–167. [Google Scholar] [CrossRef]
  83. Luna-Vázquez-Gómez, R.; Arellano-García, M.E.; Toledano-Magaña, Y.; García-Ramos, J.C.; Radilla-Chávez, P.; Salas-Vargas, D.S.; Casillas-Figueroa, F.; Ruiz-Ruiz, B.; Pestryakov, A.; Bogdanchikova, N. Bell Shape Curves of Hemolysis Induced by Silver Nanoparticles: Review and Experimental Assay. Nanomaterials 2022, 12, 1066. [Google Scholar] [CrossRef] [PubMed]
  84. Hwang, J.; Choi, D.; Han, S.; Jung, S.Y.; Choi, J.; Hong, J. Potential toxicity of polystyrene microplastic particles. Sci. Rep. 2020, 10, 7391. [Google Scholar] [CrossRef]
  85. Peetla, C.; Labhasetwar, V. Biophysical Characterization of Nanoparticle–Endothelial Model Cell Membrane Interactions. Mol. Pharm. 2008, 5, 418–429. [Google Scholar] [CrossRef] [PubMed]
  86. Peetla, C.; Labhasetwar, V. Effect of Molecular Structure of Cationic Surfactants on Biophysical Interactions of Surfactant-Modified Nanoparticles with a Model Membrane and Cellular Uptake. Langmuir 2009, 25, 2369–2377. [Google Scholar] [CrossRef] [PubMed]
  87. Saha, K.; Moyano, D.F.; Rotello, V.M. Protein coronas suppress the hemolytic activity of hydrophilic and hydrophobic nanoparticles. Mater. Horizons 2013, 1, 102–105. [Google Scholar] [CrossRef] [Green Version]
  88. Horie, M.; Tabei, Y. Role of oxidative stress in nanoparticles toxicity. Free. Radic. Res. 2020, 55, 331–342. [Google Scholar] [CrossRef]
  89. Manke, A.; Wang, L.; Rojanasakul, Y. Mechanisms of Nanoparticle-Induced Oxidative Stress and Toxicity. BioMed Res. Int. 2013, 2013, 942916. [Google Scholar] [CrossRef] [Green Version]
  90. Dayem, A.A.; Hossain, M.K.; Lee, S.B.; Kim, K.; Saha, S.K.; Yang, G.-M.; Choi, H.Y.; Cho, S.-G. The Role of Reactive Oxygen Species (ROS) in the Biological Activities of Metallic Nanoparticles. Int. J. Mol. Sci. 2017, 18, 120. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  91. Fibach, E. The Redox Balance and Membrane Shedding in RBC Production, Maturation, and Senescence. Front. Physiol. 2021, 12, 604738. [Google Scholar] [CrossRef]
  92. Fibach, E.; Rachmilewitz, E. The Role of Oxidative Stress in Hemolytic Anemia. Curr. Mol. Med. 2008, 8, 609–619. [Google Scholar] [CrossRef]
  93. Koshkaryev, A.; Yedgar, S.; Relevy, H.; Fibach, E.; Barshtein, G. Acridine orange induces translocation of phosphatidylserine to red blood cell surface. Am. J. Physiol. Physiol. 2003, 285, C720–C722. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  94. Koshkaryev, A.; Zelig, O.; Manny, N.; Yedgar, S.; Barshtein, G. Rejuvenation treatment of stored red blood cells reverses storage-induced adhesion to vascular endothelial cells. Transfusion 2009, 49, 2136–2143. [Google Scholar] [CrossRef] [PubMed]
  95. Mohanty, J.G.; Nagababu, E.; Rifkind, J.M. Red blood cell oxidative stress impairs oxygen delivery and induces red blood cell aging. Front. Physiol. 2014, 5, 84. [Google Scholar] [CrossRef] [Green Version]
  96. Ramot, Y.; Koshkaryev, A.; Goldfarb, A.; Yedgar, S.; Barshtein, G. Phenylhydrazine as a partial model for β-thalassaemia red blood cell hemodynamic properties. Br. J. Haematol. 2008, 140, 692–700. [Google Scholar] [CrossRef]
  97. Yedgar, S.; Hovav, T.; Barshtein, G. Red blood cell intercellular interactions in oxidative stress states. Clin. Hemorheol. Microcirc. 1999, 21, 189–193. [Google Scholar] [PubMed]
  98. Ben-Hur, E.; Barshtein, G.; Chen, S.; Yedgar, S. Photodynamic Treatment of Red Blood Cell Concentrates For Virus Inactivation Enhances Red Blood Cell Aggregation: Protection with Antioxidants. Photochem. Photobiol. 1997, 66, 509–512. [Google Scholar] [CrossRef]
  99. Barshtein, G.; Gural, A.; Manny, N.; Zelig, O.; Yedgar, S.; Arbell, D. Storage-induced damage to red blood cell mechanical properties can be only partially reversed by rejuvenation. Transfus. Med. Hemotherapy Off. Organ Der Dtsch. Ges. Fur Transfus. Und Immunhamatol. 2014, 41, 197–204. [Google Scholar] [CrossRef] [Green Version]
  100. Lang, F.; Abed, M.; Lang, E.; Föller, M. Oxidative Stress and Suicidal Erythrocyte Death. Antioxid. Redox Signal. 2014, 21, 138–153. [Google Scholar] [CrossRef]
  101. Vallyathan, V.; Shi, X. The role of oxygen free radicals in occupational and environmental lung diseases. Environ. Health Perspect. 1997, 105, 165–177. [Google Scholar] [CrossRef]
  102. Fubini, B.; Hubbard, A. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation by silica in inflammation and fibrosis. Free. Radic. Biol. Med. 2003, 34, 1507–1516. [Google Scholar] [CrossRef]
  103. Sztandera, K.; Gorzkiewicz, M.; Klajnert-Maculewicz, B. Gold Nanoparticles in Cancer Treatment. Mol. Pharm. 2019, 16, 1–23. [Google Scholar] [CrossRef] [PubMed]
  104. Yin, I.X.; Zhang, J.; Zhao, I.S.; Mei, M.L.; Li, Q.; Chu, C.H. The Antibacterial Mechanism of Silver Nanoparticles and Its Application in Dentistry. Int. J. Nanomed. 2020, 15, 2555–2562. [Google Scholar] [CrossRef] [Green Version]
  105. Flores-López, L.Z.; Espinoza-Gómez, H.; Somanathan, R. Silver nanoparticles: Electron transfer, reactive oxygen species, oxidative stress, beneficial and toxicological effects. Mini review. J. Appl. Toxicol. 2019, 39, 16–26. [Google Scholar] [CrossRef] [Green Version]
  106. Enea, M.; Pereira, E.; De Almeida, M.P.; Araújo, A.M.; Bastos, M.D.L.; Carmo, H. Gold Nanoparticles Induce Oxidative Stress and Apoptosis in Human Kidney Cells. Nanomaterials 2020, 10, 995. [Google Scholar] [CrossRef] [PubMed]
  107. Durán, N.; Silveira, C.; Durán, M.; Martinez, D.S.T. Silver nanoparticle protein corona and toxicity: A mini-review. J. Nanobiotechnol. 2015, 13, 55. [Google Scholar] [CrossRef] [Green Version]
  108. Yadav, S.; Maurya, P.K. Recent advances in the protective role of metallic nanoparticles in red blood cells. 3 Biotech 2022, 12, 28. [Google Scholar] [CrossRef] [PubMed]
  109. Luna-Vázquez-Gómez, R.; Arellano-García, M.; García-Ramos, J.; Radilla-Chávez, P.; Salas-Vargas, D.; Casillas-Figueroa, F.; Ruiz-Ruiz, B.; Bogdanchikova, N.; Pestryakov, A. Hemolysis of Human Erythrocytes by Argovit™ AgNPs from Healthy and Diabetic Donors: An In Vitro Study. Materials 2021, 14, 2792. [Google Scholar] [CrossRef]
  110. Barkur, S.; Lukose, J.; Chidangil, S. Probing Nanoparticle–Cell Interaction Using Micro-Raman Spectroscopy: Silver and Gold Nanoparticle-Induced Stress Effects on Optically Trapped Live Red Blood Cells. ACS Omega 2020, 5, 1439–1447. [Google Scholar] [CrossRef]
  111. Zhang, E.; Phan, P.; Algarni, H.A.; Zhao, Z. Red Blood Cell Inspired Strategies for Drug Delivery: Emerging Concepts and New Advances. Pharm. Res. 2022, 39, 2673–2698. [Google Scholar] [CrossRef] [PubMed]
  112. Glassman, P.M.; Hood, E.D.; Ferguson, L.T.; Zhao, Z.; Siegel, D.L.; Mitragotri, S.; Brenner, J.S.; Muzykantov, V.R. Red blood cells: The metamorphosis of a neglected carrier into the natural mothership for artificial nanocarriers. Adv. Drug Deliv. Rev. 2021, 178, 113992. [Google Scholar] [CrossRef]
  113. Han, X.; Wang, C.; Liu, Z. Red Blood Cells as Smart Delivery Systems. Bioconjug. Chem. 2018, 29, 852–860. [Google Scholar] [CrossRef]
  114. Rossi, G.; Barnoud, J.; Monticelli, L. Polystyrene Nanoparticles Perturb Lipid Membranes. J. Phys. Chem. Lett. 2014, 5, 241–246. [Google Scholar] [CrossRef] [PubMed]
  115. Vincy, A.; Mazumder, S.; Amrita; Banerjee, I.; Hwang, K.C.; Vankayala, R. Recent Progress in Red Blood Cells-Derived Particles as Novel Bioinspired Drug Delivery Systems: Challenges and Strategies for Clinical Translation. Front. Chem. 2022, 10, 905256. [Google Scholar] [CrossRef] [PubMed]
  116. Zhang, Y.; Bai, Y.; Jia, J.; Gao, N.; Li, Y.; Zhang, R.; Jiang, G.; Yan, B. Perturbation of physiological systems by nanoparticles. Chem. Soc. Rev. 2014, 43, 3762–3809. [Google Scholar] [CrossRef]
  117. Brenner, J.S.; Mitragotri, S.; Muzykantov, V.R. Red Blood Cell Hitchhiking: A Novel Approach for Vascular Delivery of Nanocarriers. Annu. Rev. Biomed. Eng. 2021, 23, 225–248. [Google Scholar] [CrossRef]
  118. Chambers, E.; Mitragotri, S. Prolonged circulation of large polymeric nanoparticles by non-covalent adsorption on erythrocytes. J. Control. Release 2004, 100, 111–119. [Google Scholar] [CrossRef] [PubMed]
  119. Hu, C.-M.J.; Fang, R.H.; Zhang, L. Erythrocyte-Inspired Delivery Systems. Adv. Health Mater. 2012, 1, 537–547. [Google Scholar] [CrossRef] [PubMed]
  120. Luk, B.T.; Hu, C.-M.J.; Fang, R.H.; Dehaini, D.; Carpenter, C.; Gao, W.; Zhang, L. Interfacial interactions between natural RBC membranes and synthetic polymeric nanoparticles. Nanoscale 2014, 6, 2730–2737. [Google Scholar] [CrossRef] [Green Version]
  121. Villa, C.H.; Pan, D.C.; Zaitsev, S.; Cines, D.B.; Siegel, D.L.; Muzykantov, V.R. Delivery of drugs bound to erythrocytes: New avenues for an old intravascular carrier. Ther. Deliv. 2015, 6, 795–826. [Google Scholar] [CrossRef]
  122. Villa, C.H.; Seghatchian, J.; Muzykantov, V. Drug delivery by erythrocytes: “Primum non nocere”. Transfus. Apher. Sci. 2016, 55, 275–280. [Google Scholar] [CrossRef] [Green Version]
  123. Bhateria, M.; Rachumallu, R.; Singh, R.; Bhatta, R.S. Erythrocytes-based synthetic delivery systems: Transition from conventional to novel engineering strategies. Expert Opin. Drug Deliv. 2014, 11, 1219–1236. [Google Scholar] [CrossRef]
  124. Wang, S.; Ma, S.; Li, R.; Qi, X.; Han, K.; Guo, L.; Li, X. Probing the Interaction Between Supercarrier RBC Membrane and Nanoparticles for Optimal Drug Delivery. J. Mol. Biol. 2022, 167539. [Google Scholar] [CrossRef]
  125. Li, S.-Q.; Zhu, R.-R.; Zhu, H.; Xue, M.; Sun, X.-Y.; Yao, S.-D.; Wang, S.-L. Nanotoxicity of TiO2 nanoparticles to erythrocyte in vitro. Food Chem. Toxicol. 2008, 46, 3626–3631. [Google Scholar] [CrossRef]
  126. Barshtein, G.; Tamir, I.; Yedgar, S. Red blood cell rouleaux formation in dextran solution: Dependence on polymer conformation. Eur. Biophys. J. 1998, 27, 177–181. [Google Scholar] [CrossRef] [PubMed]
  127. Barshtein, G.; Wajnblum, D.; Yedgar, S. Kinetics of Linear Rouleaux Formation Studied by Visual Monitoring of Red Cell Dynamic Organization. Biophys. J. 2000, 78, 2470–2474. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  128. Monopoli, M.P.; Åberg, C.; Salvati, A.; Dawson, K.A. Biomolecular coronas provide the biological identity of nanosized materials. Nat. Nanotechnol. 2012, 7, 779–786. [Google Scholar] [CrossRef] [PubMed]
  129. Walczyk, D.; Bombelli, F.B.; Monopoli, M.P.; Lynch, I.; Dawson, K.A. What the Cell “Sees” in Bionanoscience. J. Am. Chem. Soc. 2010, 132, 5761–5768. [Google Scholar] [CrossRef] [PubMed]
  130. Fleischer, C.C.; Payne, C.K. Nanoparticle–Cell Interactions: Molecular Structure of the Protein Corona and Cellular Outcomes. Accounts Chem. Res. 2014, 47, 2651–2659. [Google Scholar] [CrossRef]
  131. Monopoli, M.P.; Walczyk, D.; Campbell, A.; Elia, G.; Lynch, I.; Baldelli Bombelli, F.; Dawson, K.A. Physical–Chemical Aspects of Protein Corona: Relevance to in Vitro and in Vivo Biological Impacts of Nanoparticles. J. Am. Chem. Soc. 2011, 133, 2525–2534. [Google Scholar] [CrossRef]
  132. Shcharbin, D.; Ionov, M.; Abashkin, V.; Loznikova, S.; Dzmitruk, V.; Shcharbina, N.; Matusevich, L.; Milowska, K.; Gałęcki, K.; Wysocki, S.; et al. Nanoparticle corona for proteins: Mechanisms of interaction between dendrimers and proteins. Colloids Surf. B Biointerfaces 2015, 134, 377–383. [Google Scholar] [CrossRef]
  133. Cedervall, T.; Lynch, I.; Foy, M.; Berggård, T.; Donnelly, S.C.; Cagney, G.; Linse, S.; Dawson, K.A. Detailed Identification of Plasma Proteins Adsorbed on Copolymer Nanoparticles. Angew. Chem. Int. Ed. 2007, 46, 5754–5756. [Google Scholar] [CrossRef] [PubMed]
  134. Röcker, C.; Pötzl, M.; Zhang, F.; Parak, W.J.; Nienhaus, G.U. A quantitative fluorescence study of protein monolayer formation on colloidal nanoparticles. Nat. Nanotechnol. 2009, 4, 577–580. [Google Scholar] [CrossRef] [PubMed]
  135. Treuel, L.; Malissek, M.; Gebauer, J.S.; Zellner, R. The Influence of Surface Composition of Nanoparticles on their Interactions with Serum Albumin. Chem. Phys. Chem. 2010, 11, 3093–3099. [Google Scholar] [CrossRef] [PubMed]
  136. Dell’Orco, D.; Lundqvist, M.; Oslakovic, C.; Cedervall, T.; Linse, S. Modeling the Time Evolution of the Nanoparticle-Protein Corona in a Body Fluid. PLoS ONE 2010, 5, e10949. [Google Scholar] [CrossRef]
  137. Kang, S.C.; Jo, Y.J.; Bak, J.P.; Kim, K.C.; Kim, Y.S. Evaluation for protein binding affinity of maghemite and magnetite nanoparticles. J. Nanosci. Nanotechnol. 2007, 7, 3706–3708. [Google Scholar] [CrossRef] [PubMed]
  138. Vroman, L. Effect of Adsorbed Proteins on the Wettability of Hydrophilic and Hydrophobic Solids. Nature 1962, 196, 476–477. [Google Scholar] [CrossRef] [PubMed]
  139. Angioletti-Uberti, S.; Ballauff, M.; Dzubiella, J. Competitive adsorption of multiple proteins to nanoparticles: The Vroman effect revisited. Mol. Phys. 2018, 116, 3154–3163. [Google Scholar] [CrossRef]
  140. Noh, H.; Vogler, E.A. Volumetric interpretation of protein adsorption: Competition from mixtures and the Vroman effect. Biomaterials 2007, 28, 405–422. [Google Scholar] [CrossRef] [Green Version]
  141. Hirsh, S.L.; McKenzie, D.R.; Nosworthy, N.J.; Denman, J.A.; Sezerman, O.U.; Bilek, M.M. The Vroman effect: Competitive protein exchange with dynamic multilayer protein aggregates. Colloids Surf. B Biointerfaces 2013, 103, 395–404. [Google Scholar] [CrossRef]
  142. Lee, H. Molecular Modeling of Protein Corona Formation and Its Interactions with Nanoparticles and Cell Membranes for Nanomedicine Applications. Pharmaceutics 2021, 13, 637. [Google Scholar] [CrossRef]
  143. Kawaguchi, H.; Amagasa, H.; Hagiya, T.; Kimura, N.; Ohtsuka, Y. Interaction between proteins and latex particles having different surface structures. Colloids Surf. 1985, 13, 295–311. [Google Scholar] [CrossRef]
  144. Koutsoukos, P.; Mumme-Young, C.; Norde, W.; Lyklema, J. Effect of the nature of the substrate on the adsorption of human plasma albumin. Colloids Surf. 1982, 5, 93–104. [Google Scholar] [CrossRef]
  145. Blunk, T.; Hochstrasser, D.F.; Sanchez, J.-C.; Müller, B.W.; Müller, R.H. Colloidal carriers for intravenous drug targeting: Plasma protein adsorption patterns on surface-modified latex particles evaluated by two-dimensional polyacrylamide gel electrophoresis. Electrophoresis 1993, 14, 1382–1387. [Google Scholar] [CrossRef] [Green Version]
  146. Gessner, A.; Lieske, A.; Paulke, B.R.; Müller, R.H. Influence of surface charge density on protein adsorption on polymeric nanoparticles: Analysis by two-dimensional electrophoresis. Eur. J. Pharm. Biopharm. 2002, 54, 165–170. [Google Scholar] [CrossRef] [PubMed]
  147. Chambers, E.; Mitragotri, S. Long circulating nanoparticles via adhesion on red blood cells: Mechanism and extended circulation. Exp. Biol. Med. 2007, 232, 958–966. [Google Scholar]
  148. Lesniak, A.; Campbell, A.; Monopoli, M.P.; Lynch, I.; Salvati, A.; Dawson, K.A. Serum heat inactivation affects protein corona composition and nanoparticle uptake. Biomaterials 2010, 31, 9511–9518. [Google Scholar] [CrossRef] [PubMed]
  149. Kelpsiene, E.; Brandts, I.; Bernfur, K.; Ekvall, M.T.; Lundqvist, M.; Teles, M.; Cedervall, T. Protein binding on acutely toxic and non-toxic polystyrene nanoparticles during filtration by Daphnia magna. Environ. Sci. Nano 2022, 9, 2500–2509. [Google Scholar] [CrossRef]
  150. Ban, Z.; Yuan, P.; Yu, F.; Peng, T.; Zhou, Q.; Hu, X. Machine learning predicts the functional composition of the protein corona and the cellular recognition of nanoparticles. Proc. Natl. Acad. Sci. USA 2020, 117, 10492–10499. [Google Scholar] [CrossRef] [Green Version]
  151. Duan, Y.; Coreas, R.; Liu, Y.; Bitounis, D.; Zhang, Z.; Parviz, D.; Strano, M.; Demokritou, P.; Zhong, W. Prediction of protein corona on nanomaterials by machine learning using novel descriptors. NanoImpact 2020, 17, 100207. [Google Scholar] [CrossRef]
  152. Findlay, M.R.; Freitas, D.N.; Mobed-Miremadi, M.; Wheeler, K.E. Machine learning provides predictive analysis into silver nanoparticle protein corona formation from physicochemical properties. Environ. Sci. Nano 2017, 5, 64–71. [Google Scholar] [CrossRef] [Green Version]
  153. Papa, E.; Doucet, J.P.; Sangion, A.; Doucet-Panaye, A. Investigation of the influence of protein corona composition on gold nanoparticle bioactivity using machine learning approaches. SAR QSAR Environ. Res. 2016, 27, 521–538. [Google Scholar] [CrossRef]
  154. Lesniak, A.; Salvati, A.; Santos-Martinez, M.J.; Radomski, M.W.; Dawson, K.A.; Åberg, C. Nanoparticle Adhesion to the Cell Membrane and Its Effect on Nanoparticle Uptake Efficiency. J. Am. Chem. Soc. 2013, 135, 1438–1444. [Google Scholar] [CrossRef] [Green Version]
  155. Baier, G.; Costa, C.; Zeller, A.; Baumann, D.; Sayer, C.; Araujo, P.H.H.; Mailänder, V.; Musyanovych, A.; Landfester, K. BSA Adsorption on Differently Charged Polystyrene Nanoparticles using Isothermal Titration Calorimetry and the Influence on Cellular Uptake. Macromol. Biosci. 2011, 11, 628–638. [Google Scholar] [CrossRef] [PubMed]
  156. Yeo, E.L.L.; Cheah, J.U.-J.; Thong, P.S.P.; Soo, K.C.; Kah, J.C.Y. Gold Nanorods Coated with Apolipoprotein E Protein Corona for Drug Delivery. ACS Appl. Nano Mater. 2019, 2, 6220–6229. [Google Scholar] [CrossRef]
  157. Nurunnabi, M.; Khatun, Z.; Huh, K.M.; Park, S.Y.; Lee, D.Y.; Cho, K.J.; Lee, Y.-K. In Vivo Biodistribution and Toxicology of Carboxylated Graphene Quantum Dots. ACS Nano 2013, 7, 6858–6867. [Google Scholar] [CrossRef] [PubMed]
  158. Poland, C.A.; Duffin, R.; Kinloch, I.; Maynard, A.; Wallace, W.A.H.; Seaton, A.; Stone, V.; Brown, S.; MacNee, W.; Donaldson, K. Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot study. Nat. Nanotechnol. 2008, 3, 423–428. [Google Scholar] [CrossRef] [PubMed]
  159. Chen, G.; Xiong, S.; Jing, Q.; van Gestel, C.A.; van Straalen, N.M.; Roelofs, D.; Sun, L.; Qiu, H. Maternal exposure to polystyrene nanoparticles retarded fetal growth and triggered metabolic disorders of placenta and fetus in mice. Sci. Total Environ. 2022, 854, 158666. [Google Scholar] [CrossRef]
  160. Fan, X.; Wei, X.; Hu, H.; Zhang, B.; Yang, D.; Du, H.; Zhu, R.; Sun, X.; Oh, Y.; Gu, N. Effects of oral administration of polystyrene nanoplastics on plasma glucose metabolism in mice. Chemosphere 2021, 288, 132607. [Google Scholar] [CrossRef]
  161. Li, D.; Sun, W.; Jiang, X.; Yu, Z.; Xia, Y.; Cheng, S.; Mao, L.; Luo, S.; Tang, S.; Xu, S.; et al. Polystyrene nanoparticles enhance the adverse effects of di-(2-ethylhexyl) phthalate on male reproductive system in mice. Ecotoxicol. Environ. Saf. 2022, 245, 114104. [Google Scholar] [CrossRef] [PubMed]
  162. Yasin, N.A.; El-Naggar, M.E.; Ahmed, Z.S.O.; Galal, M.K.; Rashad, M.M.; Youssef, A.M.; Elleithy, E.M. Exposure to Polystyrene nanoparticles induces liver damage in rat via induction of oxidative stress and hepatocyte apoptosis. Environ. Toxicol. Pharmacol. 2022, 94, 103911. [Google Scholar] [CrossRef] [PubMed]
  163. Sukhanova, A.; Bozrova, S.; Sokolov, P.; Berestovoy, M.; Karaulov, A.; Nabiev, I. Dependence of Nanoparticle Toxicity on Their Physical and Chemical Properties. Nanoscale Res. Lett. 2018, 13, 44. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  164. Cheng, L.-C.; Jiang, X.; Wang, J.; Chen, C.; Liu, R.-S. Nano–bio effects: Interaction of nanomaterials with cells. Nanoscale 2013, 5, 3547–3569. [Google Scholar] [CrossRef] [PubMed]
  165. Yu, T.; Malugin, A.; Ghandehari, H. Impact of Silica Nanoparticle Design on Cellular Toxicity and Hemolytic Activity. ACS Nano 2011, 5, 5717–5728. [Google Scholar] [CrossRef] [PubMed]
  166. ASTM E2524-08; Standard Test Method for Analysis of Hemolytic Properties of Nanoparticles. ASTM: West Conshohocken, PE, USA, 2008.
  167. Luna, L.A.V.; Martinez, D.S.T.; Alves, O.L. Nanomaterials: From Current Methods to Biomolecular Surface Chemistry Interactions. In Nanotoxicology: Materials, Methodologies and Assessments; Durán, N., Guterres, S.S., Alves, O.L., Eds.; Springer: Sao Paulo, Brazil, 2014. [Google Scholar]
  168. A Love, S.; Thompson, J.W.; Haynes, C.L. Development of screening assays for nanoparticle toxicity assessment in human blood: Preliminary studies with charged Au nanoparticles. Nanomedicine 2012, 7, 1355–1364. [Google Scholar] [CrossRef]
  169. Zhao, Y.; Sun, X.; Zhang, G.; Trewyn, B.G.; Slowing, I.I.; Lin, V.S.-Y. Interaction of Mesoporous Silica Nanoparticles with Human Red Blood Cell Membranes: Size and Surface Effects. ACS Nano 2011, 5, 1366–1375. [Google Scholar] [CrossRef] [PubMed]
  170. Li, Y.; Liu, J.; Zhong, Y.; Zhang, D.; Wang, Z.; An, Y.-L.; Lin, M.; Gao, Z.; Zhang, J. Biocompatibility of Fe3O4@Au composite magnetic nanoparticles in vitro and in vivo. Int. J. Nanomed. 2011, 6, 2805–2819. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  171. Lu, S.; Duffin, R.; Poland, C.; Daly, P.; Murphy, F.; Drost, E.; MacNee, W.; Stone, V.; Donaldson, K. Efficacy of Simple Short-Term in Vitro Assays for Predicting the Potential of Metal Oxide Nanoparticles to Cause Pulmonary Inflammation. Environ. Health Perspect. 2009, 117, 241–247. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  172. Cho, W.-S.; Duffin, R.; Bradley, M.; Megson, I.L.; MacNee, W.; Lee, J.K.; Jeong, J.; Donaldson, K. Predictive value of in vitro assays depends on the mechanism of toxicity of metal oxide nanoparticles. Part. Fibre Toxicol. 2013, 10, 55. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  173. Arts, J.H.E.; Hadi, M.; Irfan, M.-A.; Keene, A.M.; Kreiling, R.; Lyon, D.; Maier, M.; Michel, K.; Petry, T.; Sauer, U.G.; et al. A decision-making framework for the grouping and testing of nanomaterials (DF4nanoGrouping). Regul. Toxicol. Pharmacol. 2015, 71, S1–S27. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  174. Huisjes, R.; Bogdanova, A.; van Solinge, W.W.; Schiffelers, R.M.; Kaestner, L.; van Wijk, R. Squeezing for Life–Properties of Red Blood Cell Deformability. Front. Physiol. 2018, 9, 656. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  175. Kim, M.J.; Shin, S. Toxic effects of silver nanoparticles and nanowires on erythrocyte rheology. Food Chem. Toxicol. 2014, 67, 80–86. [Google Scholar] [CrossRef] [PubMed]
  176. Lin, Y.-S.; Haynes, C.L. Impacts of Mesoporous Silica Nanoparticle Size, Pore Ordering, and Pore Integrity on Hemolytic Activity. J. Am. Chem. Soc. 2010, 132, 4834–4842. [Google Scholar] [CrossRef] [PubMed]
  177. Goudarzi, R.; Dehpour, A.R.; Partoazar, A. Nanomedicine and regenerative medicine approaches in osteoarthritis therapy. Aging Clin. Exp. Res. 2022, 34, 2305–2315. [Google Scholar] [CrossRef] [PubMed]
  178. Shan, X.; Gong, X.; Li, J.; Wen, J.; Li, Y.; Zhang, Z. Current approaches of nanomedicines in the market and various stage of clinical translation. Acta Pharm. Sin. B 2022, 12, 3028–3048. [Google Scholar] [CrossRef] [PubMed]
Micromachines 13 02091 g001 550
Figure 1. The nanoparticle-based monolayers. (a–f), scanning electron microscopy images of the different fluorescent silica nanoparticles (NPs) monolayers, constructed with 35 nm, 50 nm, 100 nm, 200 nm, 300, and 450 nm NPs, respectively. (g) Table of the mean sizes, standard deviation, and NPs surface density (number of particles per 10 µm2) corresponding to each NP size (all these data were obtained using ImageJ with manual thresholding). “Reproduced from [19]”.
Figure 1. The nanoparticle-based monolayers. (a–f), scanning electron microscopy images of the different fluorescent silica nanoparticles (NPs) monolayers, constructed with 35 nm, 50 nm, 100 nm, 200 nm, 300, and 450 nm NPs, respectively. (g) Table of the mean sizes, standard deviation, and NPs surface density (number of particles per 10 µm2) corresponding to each NP size (all these data were obtained using ImageJ with manual thresholding). “Reproduced from [19]”.
Micromachines 13 02091 g001
Micromachines 13 02091 g002 550
Figure 2. Factors that affect the hemolytic activity of nanoparticles.
Figure 2. Factors that affect the hemolytic activity of nanoparticles.
Micromachines 13 02091 g002
Table
Table 1. List of NPs and their hemolytic activity.
Table 1. List of NPs and their hemolytic activity.
#NPsSize, nm[NP] in Blood, mg/mLRef.
1PS plain50; 100; 2000.001 ÷ 0.05[51,52,53,54,55]
2Amino-modified PS50; 100; 2000.001 ÷ 0.05[56,57,58]
3Carboxyl-modified PS50; 100; 2000.001 ÷ 0.05[56,59]
4TiO215; 20; 300.02 ÷ 1.0[60,61,62]
5Fe3O410; 20; 50; 1001.5 ÷ 4.0[63,64,65]
7MgO25; 40; 601.0 ÷ 20.0[66,67]
8Gold3; 5; 50; 1000.05 ÷ 0.5[68,69,70,71]
9Silver350.020 ÷ 1.0[68,72,73,74]
10Mesoporous hollow silica60; 1100.03 ÷ 1.5[75,76,77]
11ZnO20; 500.8 ÷ 10[78,79,80]
12Selenium70–2000.0005 ÷ 0.2[32,81]
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Yedgar, S.; Barshtein, G.; Gural, A. Hemolytic Activity of Nanoparticles as a Marker of Their Hemocompatibility. Micromachines 2022, 13, 2091. https://doi.org/10.3390/mi13122091

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Yedgar S, Barshtein G, Gural A. Hemolytic Activity of Nanoparticles as a Marker of Their Hemocompatibility. Micromachines. 2022; 13(12):2091. https://doi.org/10.3390/mi13122091

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Yedgar, Saul, Gregory Barshtein, and Alexander Gural. 2022. "Hemolytic Activity of Nanoparticles as a Marker of Their Hemocompatibility" Micromachines 13, no. 12: 2091. https://doi.org/10.3390/mi13122091

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Yedgar, S., Barshtein, G., & Gural, A. (2022). Hemolytic Activity of Nanoparticles as a Marker of Their Hemocompatibility. Micromachines, 13(12), 2091. https://doi.org/10.3390/mi13122091

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