Fate Of Nanoparticles Research Articles

Prediction of the aggregation rate of nanoparticles in porous media in the diffusion-controlled regime.

The fate and aggregation of nanoparticles (NPs) in the subsurface are important due to potentially harmful impacts on the environment and human health. This study aims to investigate the effects of flow velocity, particle size, and particle concentration on the aggregation rate of NPs in a diffusion-limited regime and build an equation to predict the aggregation rate when NPs move in the pore space between randomly packed spheres (including mono-disperse, bi-disperse, and tri-disperse spheres). The flow of 0.2M potassium chloride (KCl) through the random sphere packings was simulated by the lattice Boltzmann method (LBM). The movement and aggregation of cerium oxide (CeO2) particles were then examined by using a Lagrangian particle tracking method based on a force balance approach. This method relied on Newton's second law of motion and took the interaction forces among particles into account. The aggregation rate of NPs was found to depend linearly on time, and the slope of the line was a power function of the particle concentration, the Reynolds (Re) and Schmidt (Sc) numbers. The exponent for the Sc number was triple that of the Re number, which was evidence that the random movement of NPs has a much stronger effect on the rate of diffusion-controlled aggregation than the convection.

Fate and biological uptake of polystyrene nanoparticles in freshwater wetland ecosystems

Wetland mesocosms retained nanoplastics. Nanoplastics where taken up by freshwater invertebrates and macrophytes and mainly ended up in the sediments of the water compartment.

Regulation of macrophage uptake through the bio-nano interaction using surface functionalized mesoporous silica nanoparticles with large radial pores.

Porous nanoparticles, such as mesoporous silica nanoparticles (MSNs), have garnered significant interest for biomedical applications. Recently, MSNs with large radial pores have attracted increased attention because their unique pore structure and large pore size are suitable for delivering large molecules such as proteins and genes. Upon entry into biological systems like the bloodstream, nanoparticles quickly form a 'protein corona,' leading to alterations in their interactions with immune cells. In this study, we investigated the formation of protein corona on MSNs with large radial pores and various surface modifications using mass spectrometry. We also examined the effects of protein corona on the interaction between MSNs and macrophages. We prepared MSNs with large, cone-shaped radial pores (>30 nm) and six different functional groups, resulting in nanoparticles with neutral, negative, and positive surface charges. Our findings indicate that surface functional groups significantly alter the composition of the protein corona, affecting the bio-nano interaction of these surface-modified MSNs with macrophages. Notably, nanoparticles with similar surface charges exhibited distinct corona characteristics and were internalized differently by macrophages. This underscores the crucial role of the protein corona in determining the fate, behavior, and biological responses of nanoparticles. Our research sheds light on the significance of understanding and controlling protein corona formation to optimize the design and functionality of nanoparticle-based biomedical applications.

Escape sites from the endo-lysosomal trafficking route manipulate exocytosis of nanoparticles in polar epithelium.

The endo-lysosomal pathway is a major barrier for the trans-epithelial transport of nanoparticles (NPs), but escape strategies could facilitate trans-epithelial delivery. Based on the polarization properties of the epithelium, different escape compartments may result in different exocytosis fates of NPs and further affect the delivery efficiency. Therefore, optimizing the escape sites is critical for trans-epithelial delivery. Here, commonly used PEG-coated-poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles were fabricated as model nanoparticles (MNPs) and the intestinal epithelium was chosen as the polarized epithelium. The MNPs were incubated with different endosomolytic agents for early endosomal escape, late endosomal escape and lysosomal escape, respectively. According to in vitro and in vivo studies, MNPs escaping from early endosomes and late endosomes exhibited stronger capacity for trans-epithelial transport than those escaping from lysosomes. By further probing into the mechanism, we surprisingly found that although MNPs escaping from early endosomes quickly egressed from the apical side of epithelia, they were subsequently followed by "reuptake" via caveolae and trafficked through the endoplasmic reticulum-Golgi apparatus (ER/GA) secretory pathway, achieving efficient trans-epithelial transport; MNPs escaping from late endosomes, which were located near the nucleus, were prone to enter the ER/GA for efficient basolateral exocytosis. However, MNPs escaping from lysosomes were detained within cells by autophagosomes. Collectively, our research suggested that early endosomes and late endosomes were ideal escape sites for trans-epithelial delivery.

In situ characterization techniques of protein corona around nanomaterials.

Nanoparticles (NPs) inevitably interact with proteins upon exposure to biological fluids, leading to the formation of an adsorption layer known as the "protein corona". This corona imparts NPs with a new biological identity, directly influencing their interactions with living systems and dictating their fates in vivo. Thus, gaining a comprehensive understanding of the dynamic interplay between NPs and proteins in biological fluids is crucial for predicting therapeutic effects and advancing the clinical translation of nanomedicines. Numerous methods have been established to decode the protein corona fingerprints. However, these methods primarily rely on prior isolation of NP-protein complex from the surrounding medium by centrifugation, resulting in the loss of outer-layer proteins that directly interact with the biological system and determine the in vivo fate of NPs. We discuss here separation techniques as well as in situ characterization methods tailored for comprehensively unraveling the inherent complexities of NP-protein interactions, highlighting the challenges of in situ protein corona characterization and its significance for nanomedicine development and clinical translation.

Shape-dependent cellular uptake of iron oxide nanorods: mechanisms of endocytosis and implications on cell labeling and cellular delivery.

The effects of nanoparticle morphology, especially size and shape, on their interactions with cells are of great interest in understanding the fate of nanoparticles in biological systems and designing them for biomedical applications. While size and shape-dependent cell behavior, endocytosis mechanism, and subcellular distribution of nanoparticles have been investigated extensively with gold and other nanoparticles, studies on iron oxide nanoparticles (IONP), one of the most promising and well-thought-of nanomaterials in biomedical applications, were limited. In this study, we synthesized oligosaccharide-coated water-soluble iron oxide nanorods (IONR) with different core sizes (nm) and different aspect ratios (i.e., length/width), such as IONR(L) at 140/6 nm and IONR(S) at 50/7 nm as well as spherical IONP (20 nm). We investigated how their sizes and shapes affect uptake mechanisms, localization, and cell viability in different cell lines. The results of transmission electron microscopy (TEM) and confocal fluorescence microscopic imaging confirmed the internalization of these nanoparticles in different types of cells and subsequent accumulation in the subcellular compartments, such as the endosomes, and into the cytosol. Specifically, IONR(L) exhibited the highest cellular uptake compared to IONR(S) and spherical IONP, 1.36-fold and 1.17-fold higher than that of spherical IONP in macrophages and pediatric brain tumor medulloblastoma cells, respectively. To examine the cellular uptake mechanisms preferred by the different IONR and IONP, we used different endocytosis inhibitors to block specific cellular internalization pathways when cells were treated with different nanoparticles. The results from these blocking experiments showed that IONR(L) enter macrophages and normal kidney cells through clathrin-mediated, dynamin-dependent, and macropinocytosis/phagocytosis pathways, while they are internalized in cancer cells primarily via clathrin/caveolae-mediated and phagocytosis mechanisms. Overall, our findings provide new insights into further development of magnetic IONR-based imaging probes and drug delivery systems for biomedical applications.

Fluorescent Labeling and Imaging of IL-22 mRNA-Loaded Lipid Nanoparticles.

Lipid nanoparticle (LNP)-based drug delivery systems (DDSs) are widely recognized for their ability to enhance efficient and precise delivery of therapeutic agents, including nucleic acids like DNA and mRNA. Despite this acknowledgment, there is a notable knowledge gap regarding the systemic biodistribution and organ accumulation of these nanoparticles. The ability to track LNPs in vivo is crucial for understanding their fate within biological systems. Fluorescent labeling of LNPs facilitates real-time tracking, quantification, and visualization of their behavior within biological systems, providing valuable insights into biodistribution, cellular uptake, and the optimization of drug delivery strategies. Our prior research established reversely engineered LNPs as an exceptional mRNA delivery platform for treating ulcerative colitis. This study presents a detailed protocol for labeling interleukin-22 (IL-22) mRNA-loaded LNPs, their oral administration to mice, and visualization of DiR-labeled LNPs biodistribution in the gastrointestinal tract using IVIS spectrum. This fluorescence-based approach will assist researchers in gaining a dynamic understanding of nanoparticle fate in other models of interest. Key features • This protocol is developed to assess the delivery of IL-22 mRNA to ulcerative colitis sites using lipid nanoparticles. • This protocol uses fluorescent DiR dye for imaging of IL-22 mRNA-loaded lipid nanoparticles in the gastrointestinal tract of mice. • This protocol employs the IVIS spectrum for imaging.

Intracerebral fate of organic and inorganic nanoparticles is dependent on microglial extracellular vesicle function.

Nanoparticles (NPs) represent an important advance for delivering diagnostic and therapeutic agents across the blood-brain barrier. However, NP clearance is critical for safety and therapeutic applicability. Here we report on a study of the clearance of model organic and inorganic NPs from the brain. We find that microglial extracellular vesicles (EVs) play a crucial role in the clearance of inorganic and organic NPs from the brain. Inorganic NPs, unlike organic NPs, perturb the biogenesis of microglial EVs through the inhibition of ERK1/2 signalling. This increases the accumulation of inorganic NPs in microglia, hindering their elimination via the paravascular route. We also demonstrate that stimulating the release of microglial EVs by an ERK1/2 activator increased the paravascular glymphatic pathway-mediated brain clearance of inorganic NPs. These findings highlight the modulatory role of microglial EVs on the distinct patterns of the clearance of organic and inorganic NPs from the brain and provide a strategy for modulating the intracerebral fate of NPs.

Aggregation behavior of polystyrene nanoplastics: Role of surface functional groups and protein and electrolyte variation

Aggregation kinetics of plastics are affected by the surface functional groups and exposure orders (electrolyte and protein) with kinds of mechanisms in aquatic environment. This study investigates the aggregation of polystyrene nanoplastics (PSNPs) with varying surface functional groups in the presence of common electrolytes (NaCl, CaCl2, Na2SO4) and bovine serum albumin (BSA). It also examines the impact of different exposure orders, namely BSA + NaCl (adding them together), BSA → NaCl (adding BSA firstly and then NaCl), and NaCl → BSA (adding NaCl firstly and then BSA), on PSNPs aggregation. The presence of BSA decreased the critical coagulation concentration in NaCl (CCCNa+) of the non-modified PS-Bare from 222.17 to 142.81 mM (35.72%), but increased that of the carboxyl-modified PS-COOH from 157.34 to 160.03 mM (1.71%). This might be ascribed to the thicker absorbed layer of BSA onto the PS-Bare surface, known from Ohshima's soft particle theory. Their aggregation in CaCl2 was both increased because of Ca2+ bridging. Different from the monotonous effects of BSA on PS-Bare and PS-COOH, BSA initially facilitated PS-NH2 aggregation via patch-charge attraction, then inhibited it at higher salt levels through steric repulsion. Furthermore, exposure orders had no significant effect on PS-Bare and PS-COOH, but had a NaCl concentration-dependent impact on PS-NH2. At the low NaCl concentrations (10 and 100 mM), no obvious influence could be observed. While, at 300 mM NaCl, the high concentrations of BSA could not totally stabilize the salt-induced aggregates in NaCl → BSA, but could achieve it in the other two orders. These might be attributed to the electrical double layer compression by NaCl, “patch-charge” force and steric hindrance by BSA. These experimental findings shed light on the potential fate and transport of nanoparticles in aquatic environments.

Visualizing the intracellular aggregation behavior of gold nanoclusters via structured illumination microscopy and scanning transmission electron microscopy

Given the growing concerns about nanotoxicity, numerous studies have focused on providing mechanistic insights into nanotoxicity by imaging the intracellular fate of nanoparticles. A suitable imaging strategy is necessary to uncover the intracellular behavior of nanoparticles. Although each conventional technique has its own limitations, scanning transmission electron microscopy (STEM) and three-dimensional structured illumination microscopy (3D-SIM) combine the advantages of chemical element mapping, ultrastructural analysis, and cell dynamic tracking. Gold nanoclusters (AuNCs), synthesized using 6-aza-2 thiothymine (ATT) and L-arginine (Arg) as reducing and protecting ligands, referred to as Arg@ATT-AuNCs, have been widely used in biological sensing and imaging, medicine, and catalyst yield. Based on their intrinsic fluorescence and high electron density, Arg@ATT-AuNCs were selected as a model. STEM imaging showed that both the single-particle and aggregated states of Arg@ATT-AuNCs were compartmentally distributed within a single cell. Real-time 3D-SIM imaging showed that the fluorescent Arg@ATT-AuNCs gradually aggregated after being located in the lysosomes of living cells, causing lysosomal damage. The aggregate formation of Arg@ATT-AuNCs was triggered by the low-pH medium, particularly in the lysosomal acidic environment. The proposed dual imaging strategy was verified using other types of AuNCs, which is valuable for studying nano-cell interactions and any associated cytotoxicity, and has the potential to be a useful approach for exploring the interaction of cells with various nanoparticles.

Formation of extracellular polymeric substances corona on TiO2 nanoparticles: Roles of crystalline phase and exposed facets

Nanoparticles (NPs) in the environment can interact with macromolecules in the surrounding environment to form eco-corona on their surfaces, which in turn affects the environmental fate and toxicity of nanoparticles. Wastewater treatment plants containing large amounts of microbial extracellular polymeric substances (EPS) are an important source of NPs into the environment, where the formation of EPS coronas on NPs is critical. However, it remains unclear how the crystalline phase and exposed facets, which are intrinsic properties of NPs, affect the formation of EPS coronas on NPs. This study investigated the formation of EPS corona on three TiO2 NPs (representing the most widely used engineered NPs) with different crystalline phases and exposed facets. The protein type and abundance in EPS coronas on TiO2 NPs varied depending on the crystalline phase and exposed facets. Anatase with {101} facets and {001} facets preferred to adsorb proteins with lower molecular weights and higher H-bonding relevant amino acids, respectively, while EPS corona on rutile with {110} facets had proteins with higher hydrophobicity. In addition, the selective adsorption of proteins was primarily determined by steric hindrance, hydrogen bonding, and hydrophobic interaction between TiO2 NPs and proteins, which were affected by changes in aggregation state, surface hydroxyl density, and hydrophobicity of TiO2 NPs induced by crystalline phase and exposed facets. Moreover, crystalline phase and exposed facets-induced EPS corona changes altered the aggregation state and oxidation potential of TiO2–EPS corona complexes. These findings emphasize the important role of crystalline phase and exposed facets in the environmental behavior of nanoparticles and may provide insights into the safe design of nanoparticles.

Impact of calcium ions at physiological concentrations on the adsorption behavior of proteins on silica nanoparticles

The adsorption of proteins on nanoparticles (NPs) largely decides the fate and bioeffects of NPs in vivo. However, bio-fluids are too complicated to directly study in them to reveal related mechanisms, and current studies on model systems often ignore some important biological factors, such as metal ions. Herein, we evaluate the effect of Ca2+ at physiological concentrations on the protein adsorption on negatively-charged silica NP (SNP50). It is found that Ca2+, as well as Mg2+ and several transition metal ions, significantly enhances the adsorption of negatively-charged proteins on SNP50. Moreover, the Ca2+-induced enhancement of protein adsorption leads to the reduced uptake of SNP50 by HeLa cells. A double-chelating mechanism is proposed for the enhanced adsorption of negatively-charged proteins by multivalent metal ions that can form 6 (or more) coordinate bonds, where the metal ions are chelated by both the surface groups of NPs and the surface residues of the adsorbed proteins. This mechanism is consistent with all experimental evidences from metal ions-induced changes of physicochemical properties of NPs to protein adsorption isotherms, and is validated with several model proteins as well as complicated serum. The findings highlight the importance of investigating the influences of physiological factors on the interaction between proteins and NPs.

Characterisation and functionalisation of chitosan nanoparticles as carriers for double-stranded RNA (dsRNA) molecules towards sustainable crop protection.

The need to minimise the impact of phytosanitary treatments for disease control boosted researchers to implement techniques with less environmental impact. The development of technologies using molecular mechanisms based on the modulation of metabolism by short dsRNA sequences appears promising. The intrinsic fragility of polynucleotides and the high cost of these techniques can be circumvented by nanocarriers that protect the bioactive molecule enabling high efficiency delivery to the leaf surface and extending its half-life. In this work, a specific protocol was developed aiming to assess the best methodological conditions for the synthesis of low-size chitosan nanoparticles (NPs) to be loaded with nucleotides. In particular, NPs have been functionalised with partially purified Green Fluorescent Protein dsRNAs (GFP dsRNA) and their size, surface charge and nucleotide retention capacity were analysed. Final NPs were also stained with FITC and sprayed on Nicotiana benthamiana leaves to assess, by confocal microscopy, both a distribution protocol and the fate of NPs up to 6 days after application. Finally, to confirm the ability of NPs to increase the efficacy of dsRNA interference, specific tests were performed: by means of GFP dsRNA-functionalised NPs, the nucleotide permanence during time was assessed both in vitro on detached wild-type N. benthamiana leaves and in planta; lastly, the inhibition of Botrytis cinerea on single leaves was also evaluated, using a specific fungal sequence (Bc dsRNA) as the NPs' functionalising agent. The encouraging results obtained are promising in the perspective of long-lasting application of innovative treatments based on gene silencing.

Piperlongumine based nanomedicine impairs glycolytic metabolism in triple negative breast cancer stem cells through modulation of GAPDH & FBP1

BackgroundTriple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and exhibits high rate of chemoresistance, metastasis, and relapse. This can be attributed to the failure of conventional therapeutics to target a sub-population of slow cycling or quiescent cells called as cancer stem cells (CSCs). Therefore, elimination of CSCs is essential for effective TNBC treatment. PurposeResearch suggests that breast CSCs exhibit elevated glycolytic metabolism which directly contributes in maintenance of stemness, self-renewability and chemoresistance as well as in tumor progression. Therefore, this study aimed to target rewired metabolism which can serve as Achilles heel for CSCs population and have far reaching effect in TNBC treatment. MethodsWe used two preclinical models, zebrafish and nude mice to evaluate the fate of nanoparticles as well as the therapeutic efficacy of both piperlongumine (PL) and its nanomedicine (PL-NPs). ResultsIn this context, we explored a phytochemical piperlongumine (PL) which has potent anti-cancer properties but poor pharmacokinetics impedes its clinical translation. So, we developed PLGA based nanomedicine for PL (PL-NPs), and demonstrated that it overcomes the pharmacokinetic limitations of PL, along with imparting advantages of selective tumor targeting through Enhanced Permeability and Retention (EPR) effect in zebrafish xenograft model. Further, we demonstrated that PL-NPs efficiently inhibit glycolysis in CSCs through inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by modulating glutathione S-transferase pi 1 (GSTP1) and upregulation of fructose-1,6-bisphosphatase 1 (FBP1), a rate-limiting enzyme in gluconeogenesis. We also illustrated that inhibition of glycolysis results in overall tumor regression in two preclinical models. ConclusionThis study discusses novel mechanism of action by which PL acts on CSCSs. Taken together our study provides insight into development of PL based nanomedicine which could be exploited in clinics to achieve complete eradication of TNBC by targeting CSCs.

Application of Microorganisms as Biofactories to Produce Biogenic Nanoparticles for Environmental Cleanup: Currents Advances and Challenges

Abstract: Recently, there has been a significant increase in the rate and amount of pollutant discharge into the environment. This is extremely worrisome to the human population, especially as it is envisaged to reach 10 billion in the next 40 years. The traditional methods applied for pollutant abatement and recycling exhibit inefficiency and environmental unfriendliness because they cannot effectively transform these pollutants into non-noxious states. Recently, microorganisms and nano-based materials are emerging as highly efficient and eco-friendly alternatives for managing, reducing, and decontaminating pollutant wastes or effluents in the environment. The biosynthesis of these materials has motivated research into developing cheaper, green, and more sustainable yeast, algae, fungi, and bacteria-biogenic nanoparticles, which could be used to clean up heavily contaminated environments. This review evaluates the application of microorganisms (yeast, algae, fungi, and bacteria) with nanomaterials as biogenic nanoparticles to clean up environmental pollutants. The environmental and health hazards associated with the fate of the biogenic nanoparticles, and some legal regulations, are also highlighted. The commercialization of nanomaterials and their possible global application are also documented. Future recommendations were proffered.

Kinetics and Timescales in Bio–Nano Interactions

Engineered nanoparticles (NPs) have the potential to revolutionize disease diagnostics and treatment. However, NP interactions with proteins in biological fluids complicate their in vivo control. These interactions often lead to the formation of protein coronas around the NP surface, shaping NP fate and behavior within biological systems. To harness the full potential of NPs in biomedical applications, it is therefore essential to gain a comprehensive understanding of their interactions with proteins. Within this context, it must be recognized that traditional equilibrium-based descriptions of NP–protein interactions, which encompass parameters like equilibrium binding affinity and corona composition, do not provide sufficient detail to predict NP behavior in vivo. This limitation arises because the open in vivo system is a nonequilibrium state characterized by constantly changing concentrations and dynamic regulation of biological processes. In light of these considerations, this review explores the kinetics and timescales of NP–protein interactions, discussing their relevance, fundamental concepts, measurement techniques, typical ranges of association and dissociation rate constants, and dynamics of protein corona formation and dissociation. The review concludes by outlining potential areas for further research and development in this field.

Fate of iron nanoparticles in anammox system: Dissolution, migration and transformation

Iron nanoparticles (FeNPs) are commonly used in various industrial processes, leading to their release into the environment and eventual entrance into wastewater treatment plants (WWTPs). FeNPs undergo dissolution, migration, and transformation in WWTPs, which can potentially affect the stable operation of anaerobic ammonia oxidation (anammox) systems and may be discharged with wastewater or biomass. To better understand the fate of FeNPs in anammox systems, exposure experiments were conducted using anammox granular sludges (AnGS) and FeNPs. Results demonstrated that FeNPs released Fe2+ upon contact with water, with a portion being bound to functional groups in extracellular polymeric substances (EPS) and the rest entering the bacteria to form highly absorbable substances. A significant amount of FeNPs was observed to cover the surface of AnGS or aggregate and deposit at the bottom of the reactor, eventually converting into Fe3O4 and stably existing within the anammox system. The findings of this study clarify the fate of FeNPs in anammox systems and provide important insights into the stable operation of anammox systems under FeNPs exposure.

Label-Free Quantification of Digital Nanorods Assembled from Discrete Oligourethane Amphiphiles.

Polymeric nanoparticles (NPs) have been extensively designed for theranostic agent delivery. Previous methods for tracking their biological behavior and assessing theranostic efficacy heavily rely on fluorescence or isotope labeling. However, these labeling techniques may alter the physicochemical properties of the labeled NPs, leading to inaccurate biodistribution information. Therefore, it is highly desirable to develop label-free techniques for accurately assessing the biological fate of polymeric NPs. Here, we create discrete oligourethane amphiphiles (DOAs) with methoxy (OMe), hydroxyl (OH), and maleimide (MI) moieties at the dendritic oligo(ethylene glycol) (dOEG) ends. We obtained four types of digital nanorods (NRs) with distinct surface functional groups through self-assembly of a single DOA (OMe and OH NRs) or coassembly of two DOAs (OMe-MI and OH-MI NRs). These unique NRs can be directly quantified in a label-free manner by using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Specifically, OMe-MI NRs exhibited the best blood circulation, and OH-MI showed the highest area under the curve (AUC) value after intravenous injection. Biodistribution studies demonstrated that MI-containing NRs generally had lower accumulation in the liver and spleen compared to that of MI-free NRs, except for the comparison between OMe and OMe-MI NRs in the liver. Proteomics studies unveiled the formation of distinct protein coronas that may greatly affect the biological behavior of NRs. This study not only provides a label-free technique for quantifying the pharmacokinetics and biodistribution of polymeric NRs but also highlights the significant impact of surface functional groups on the biological fate of polymeric NPs.

MRI Directed Magnevist Effective to Study Toxicity of Gd-Doped Mesoporous Carbon Nanoparticles in Mice Model.

Magnetic resonance imaging (MRI) has been a valuable and widely used examination technique in clinical diagnosis and prognostic efficacy evaluation. The introduction of MRI contrast agent (CA) improves its sensitivity obviously, particularly with the development of nano-CA, which presents higher contrast enhancement ability. However, systematical evaluation of their toxicity is still limited, hampering their further translation in clinics. In this paper, to systematically evaluate the toxicity of nano-CA, Gd-doped mesoporous carbon nanoparticles (Gd-MCNs) prepared by a one-step hard template method were introduced as a model and clinically used MRI CA, Magnevist (Gd-DTPA) as control. Their in vitro blood compatibility, cellular toxicity, DNA damage, oxidative stress, inflammation response as well as in vivo toxicity and MR imaging behaviors were studied and compared. The experimental results showed that compared with Gd-DTPA, Gd-MCNs displayed negligible influence on the red blood cell shape, aggregation, BSA structure, macrophage morphology and mitochondrial function. Meanwhile, limited ROS and inflammatory cytokine production also illustrated the cellular compatibility of Gd-MCNs. For in vivo toxicity evaluation, Gd-MCNs presented acceptable in vivo biosafety even under 12 times injection for 12 weeks. More importantly, at the same concentration of Gd, Gd-MCNs displayed better contrast enhancement of tumor than Gd-DTPA, mainly coming from its high MRI relaxation rate which is nearly 9 times that of Gd-DTPA. In this paper, we focus on the toxicity evaluation of MRI nano-CA, Gd-MCNs from different angles. With Gd-DTPA as control, Gd-MCNs appeared to be highly biocompatible and safe nanoparticles that possessed promising potentials for the use of MRI nano-CA. In the future, more research on the long-term genotoxicity and the fate of nanoparticles after being swallowed should be performed.

Growth patterns of Pseudomonas aeruginosa in milk fortified with chitosan and selenium nanoparticles during refrigerated storage

Pseudomonas spp are considered a common milk-associated psychotropic bacteria, leading to milk deterioration during storage; therefore, our study aimed to study the distribution of Pseudomonas aeruginosa in raw milk and its associated products then studying the growth behavior of P. aeruginosa in milk after employing chitosan nanoparticles (CsNPs 50, 25, and 15 mg/100ml) and selenium nanoparticles (SeNPs 0.5, 0.3 and 0.1 mg/100ml) as a trial to control the bacterial growth in milk during five days of cooling storage. Our study relies on the ion gelation method and green synthesis for the conversion of chitosan and selenium to nanosized particles respectively, we subsequently confirmed their shape using SEM and TEM. We employing Pseudomonas selective agar medium for monitoring the bacterial growth along the cooling storage. Our findings reported that high prevalence of Pseudomonas spp count in raw milk and kareish cheese and high incidence percent of P. aeruginosa in ice cream and yogurt respectively. Both synthesized nanoparticles exhibited antibacterial activity in a dose-dependent manner. Moreover, CsNPs50 could inhibit the P. aeruginosa survival growth to a mean average of 2.62 ± 1.18 log10cfu/ml in the fifth day of milk cooling storage; also, it was noted that the hexagonal particles SeNPs0.5 could inhibit 2.49 ± 11 log10cfu/ml in comparison to the control P. aeruginosa milk group exhibited growth survival rate 7.24 ± 2.57 log10cfu/ml under the same conditions. In conclusion, we suggest employing chitosan and selenium nanoparticles to improve milk safety and recommend future studies for the fate of nanoparticles in milk.