Nanoparticles In Tissues Research Articles

The influence of Au-based nanoparticles on some physiological, biochemical and molecular characteristics of wheat plants during low temperature hardening

One of the most significant problems of the 21st century is the anthropogenic strain on the environment. The development of nanotechnology makes it possible to produce a variety of nanomaterials widely used in people's daily lives. However, nanomaterials can accumulate in ecosystems and spread through food chains. The environmental risks of nanoparticle proliferation are unclear. At the same time, certain nanoparticles act as adaptogens, improving plant tolerance to unfavorable stress factors. It is quite realistic to choose such experimental conditions, under which the effect on plant stress tolerance will be obvious and the accumulation of nanoparticles in tissues will be minimal. In this case, the main relevant factors are the type of nanoparticles, their concentration and their way of penetration into plants. We chose to study gold nanoparticles (Au-NPs), widely used in biomedical research. The concentration of Au-NPs was 20 μg/mL, which is considered safe for living organisms. The influence of Au-NPs on some physiological, biochemical and molecular characteristics of wheat plants during low temperature hardening was examined. The study of the photosynthetic apparatus and antioxidant system was the primary focus. The stimulating effect of Au-NPs on cold tolerance of wheat plants was shown. The results expand our knowledge of the processes by which nanoparticles impact plants and the potential applications of nanoparticles as adaptogens in science and agriculture.

A Low-Cost, Tabletop LOD-EPR System for Nondestructive Quantification of Iron Oxide Nanoparticles in Tissues.

Iron oxide nanoparticles (IONPs) have wide utility in applications from drug delivery to the rewarming of cryopreserved tissues. Due to the complex behavior of IONPs (e.g., uneven particle distribution and aggregation), further developments and clinical translation can be accelerated by having access to a noninvasive method for tissue IONP quantification. Currently, there is no low-cost method to nondestructively track IONPs in tissues across a wide range of concentrations. This work describes the performance of a low-cost, tabletop, longitudinally detected electron paramagnetic resonance (LOD-EPR) system to address this issue in the field of cryopreservation, which utilizes IONPs for rewarming of rat kidneys. A low-cost LOD-EPR system is realized via simultaneous transmit and receive using MHz continuous-wave transverse excitation with kHz modulation, which is longitudinally detected at the modulation frequency to provide both geometric and frequency isolation. The accuracy of LOD-EPR for IONP quantification is compared with NMR relaxometry. Solution measurements show excellent linearity (R2 > 0.99) versus Fe concentration for both measurements on EMG308 (a commercial nanoparticle), silica-coated EMG308, and PEG-coated EMG308 in water. The LOD-EPR signal intensity and NMR longitudinal relaxation rate constant (R1) of water are affected by particle coating, solution viscosity, and particle aggregation. R1 remains linear but with a reduced slope when in cryoprotective agent (CPA) solution, whereas the LOD-EPR signal is relatively insensitive to this. R1 does not correlate well with Fe concentration in rat kidney sections (R2 = 0.3487), while LOD-EPR does (R2 = 0.8276), with a linear regression closely matching that observed in solution and CPA.

Assessment of the neurotoxic effect of iron (III) oxide nanoparticles at the subcellular level

Introduction. Both naturally occurring and artificially produced nanoparticles are ubiquitous; their high concentrations can be detected in the environment, thus posing risks of toxic effects in humans. Penetrating the blood-brain barrier by metal nanoparticles has been already proven and is currently of interest from the point of view of toxicology and hygiene.
 Materials and methods. Female rats were exposed to ferric oxide nanoparticles administered intranasally with a 25 mg/ml suspension at a dose of 50 µl three times a week during six weeks. The experimental and control groups contained seven animals each. Tissue samples for testing were taken from the olfactory bulbs of the rat’s brain. Iron (III) oxide nanoparticles were identified by electron microscopy and energy-dispersive X-ray spectroscopy. The cytotoxic effect of ferric oxide nanoparticles was assessed by ranking mitochondria by mitochondrial membrane morphotypes and comparing their distribution in the experimental and control groups.
 Results. We confirmed the presence of nanoparticles in tissues of the olfactory bulbs of the exposed rodents. The morphotype pattern of mitochondria showed significant changes following the exposure to ferric oxide nanoparticles: the proportion of mitochondria with normal and vesicular swollen morphotypes decreased by 36.4 and 4.9%, respectively, compared with the control group of animals, the proportion of mitochondria with normal vesicular and vesicular morphotypes increased by 19.8 and 21.8%, while the proportion of vesicular swollen mitochondria decreased from 9.5% to 4.6%.
 Limitations. The study was limited to examining ultrastructural changes in mitochondria and identifying ferric oxide nanoparticles in tissues.
 Conclusions. Further studies of the impact of iron-containing nanoparticles on the structure and functions of the mitochondrial apparatus can help to identify their potential harm at the subcellular level and provide information for the development of appropriate health protective measures and new strategies for prevention and treatment of metal toxicity-induced diseases in humans.

Label-Free Tracking of Nanoprodrug Cellular Uptake and Metabolism Using Raman and Autofluorescence Imaging.

Nano-DDS, a drug delivery system using nanoparticles, is a promising tool to reduce adverse drug reactions and maximize drug efficiency. Understanding the intracellular dynamics following the accumulation of nanoparticles in tissues, such as cellular uptake, distribution, metabolism, and pharmacological effects, is essential to maximize drug efficiency; however, it remains elusive. In this study, we tracked the intracellular behavior of nanoparticles of a prodrug, cholesterol-linked SN-38 (CLS), in a label-free manner using Raman and autofluorescence imaging. Bright autofluorescent spots were observed in cells treated with CLS nanoparticles, and the color tone of the bright spots changed with incubation time. The Raman spectra of the bright spots showed that the autofluorescence came from the nanoparticles taken into cells, and the change in color of bright spots indicated that CLS turned into SN-38 via hydrolysis inside a cell. It was found that most of the SN-38 were localized in small regions in the cytoplasm even after the conversion from CLS, and only a small amount of SN-38 was dissolved and migrated into other cytoplasm regions and the nucleus. The massive size growth of cells was observed within several tens of hours after the treatment with CLS nanoparticles. Moreover, Raman images of cells using the cytochrome c band and the fluorescence images of cells stained with JC-1 showed that cellular uptake of CLS nanoparticles efficiently caused mitochondrial damage. These results show that the combination of Raman and autofluorescence imaging can provide insight into the intracellular behavior of prodrug nanoparticles and the cell response and facilitate the development of nano-DDSs.

Calibration Strategy to Size and Localize Multi-Shaped Nanoparticles in Tissue Sections Using LA-spICP-MS.

In the field of nanotoxicology, the detection and size characterization of nanoparticles (NPs) in biological tissues become increasingly important. To gain information on both particle size and particle distribution in histological sections, laser ablation and single particle inductively coupled plasma-mass spectrometry (LA-spICP-MS) was used in combination with a liquid calibration of dissolved metal standards via a pneumatic nebulizer. In the first step, the particle size distribution of Ag NPs embedded in matrix-matched gelatine standards introduced via LA was compared with that of Ag NPs in a suspension and nebulizer-based ICP-MS. The data show that the particles remained intact by the ablation process as confirmed by transmission electron microscopy. Moreover, the optimized method was applied to CeO2 NPs that are highly relevant for (eco-)toxicological research but, unlike Ag NPs, are multi-shaped and have a broad particle size distribution. Upon analyzing the particle size distribution of CeO2 NPs in cryosections of rat spleen, CeO2 NPs were found to remain unchanged in size over 3 h, 3 d, and 3 weeks post-intratracheal instillation, with the fraction of smaller particles reaching the spleen first. Overall, LA-spICP-MS combined with a calibration based on dissolved metal standards is a powerful tool to simultaneously localize and size NPs in histological sections in the absence of particle standards.

Evidence of polystyrene nanoplastic contamination and potential impacts in Mya arenaria clams in the Saint-Lawrence estuary (Canada)

Plastic materials found in the environment are expected to degrade into smaller plastic nanoparticles (NPs) posing a greater toxic risk because they sorb contaminants and pass physiological barriers. Moreover the presence and effects of NPs is difficult to tease out from the contamination background at polluted sites. The purpose of this study was to examine for the presence of polystyrene NPs in feral Mya arenaria clam population near anthropogenic sources of pollution and potential toxic effects. Polystyrene NPs were determined by a newly developed fluorescence-based and size exclusion chromatography methodologies. Clam health status was determined by following changes in air survival time, condition factor, growth, alcohol/aldehyde dehydrogenase (AADH), protein aggregation and lactate dehydrogenase (LDH). In addition, multi-elemental analysis in tissues was also determined. The results revealed that clams collected at 2 polluted sites contained elevated amounts of polystyrene-like NPs between 10 and 110 nm in size based on size exclusion chromatography. Elevated levels of AADH suggest the presence of hydroxylated products and were correlated with plastic NPs in tissues. Moreover, principal component analysis revealed that As, Ca, Cu, Sn and V were closely related to either polystyrene-like NPs in tissues or AADH activity. Although we cannot rule out other pollutants, clams contaminated by polystyrene-like NPs had lower condition, growth rate, air survival time and LDH activity. Increased metal/element contamination reported to sorb onto plastic polymers were also related to NPs in tissues. In conclusion, clams populations close to anthropogenic sources of pollution show evidence of polystyrene-like NPs contamination and could contribute to decreased clam health status.

Influence of alternating magnetic field on non-newtonian blood perfusion and transport of nanoparticles in tissues with embedded blood vessel during hyperthermia

In this paper, we consider the impact of an alternating magnetic field on axisymmetric non-Newtonian nanofluid flow and nanoparticle (magnetite or iron-platinum) transport through a blood vessel and surrounding tissue during hyperthermia therapy. The geometrical domain of the problem is divided into four regions; the blood vessel region, cancerous and non-cancerous muscle or prostate regions, and a fat region. Each of the tissue regions is considered to be a saturated porous material that admits fluid flow, which is given by the Darcy-Brinkman-Forchheimer model. The Quemada model is used to describe the non-Newtonian nature of blood in each region. The resulting unsteady coupled governing equations and corresponding boundary and initial conditions are numerically solved by using the finite element method with Taylor-Hood elements. A physically realistic range of parameter values are used when numerically solving the governing equations. Using the obtained numerical solution, the effects of magnetic field amplitude and oscillation frequency, inlet nanoparticle solid volume fraction and nanoparticle diameter on nanofluid velocity, temperature, pressure and nanoparticle distribution are examined. The results determined that more heat generation is achieved with a larger volume fraction of injected nanoparticles and higher magnetic field amplitude. Also, heat generation is maximized by using nanoparticles with a diameter near 15nm and a magnetic field oscillation frequency near 4×104s-1. Thus, the present study provides an improved understanding of the factors influencing the effectiveness of intravenous magnetic hyperthermia cancer therapy in muscle and prostate tissues. The heat generated by the considered nanoparticles under an alternating magnetic field can be more accurately predicted and controlled using the two-phase non-Newtonian model of fluid flow and convective heat and mass transfer that is investigated herein.

Facile preparation of indocyanine green and tiny gold nanoclusters co-loaded nanocapsules for targeted synergistic sono-/photo-therapy

Photothermal therapy (PTT) and sono-photodynamic therapy (SPDT) are fast growing local treatment modalities with minimal invasiveness and high safety. Gold nanoparticles and indocyanine green (ICG) have been used as sensitizers for PTT and SPDT. However, long resident time of gold nanoparticles in tissues and fast elimination of ICG hampered their further clinical applications. Herein, we developed nanocapsules formed by hyaluronic acid and chitosan loading with ICG and tiny gold nanoclusters (TAuNCs) to overcome the shortcomings of gold nanoparticles and ICG for combined PTT and SPDT. The nanocapsules exhibited good biological stability, favorable photothermal effects, and ultrasound/near-infrared light (NIR)-responsive release behaviors. The hyaluronic acid could mediate the specific delivery of cargos to CD44 protein over-expressing cancer cells. The in vitro and in vivo results showed that TAuNCs and ICG could act synergistically to obtain satisfactory anticancer effects under NIR laser and/or ultrasound exposure induced by thermal ablation and reactive oxygen species (ROS) generation. Biodistribution and excretion studies showed that the nanocapsules had longer ICG retention time in tumor and most of the TAuNCs could be effectively excreted from the body within one month. This study thus provides a facile strategy for the development of a safe and high-performance nanoplatform for synergistic PTT/SPDT.

Tomographic Imaging and Localization of Nanoparticles in Tissue Using Surface-Enhanced Spatially Offset Raman Spectroscopy.

A fundamental question crucial to surface-enhanced spatially offset Raman spectroscopy (SESORS) imaging and implementing it in a clinical setting for in vivo diagnostic purposes is whether a SESORS image can be used to determine the exact location of an object within tissue? To address this question, multiple experimental factors pertaining to the optical setup in imaging experiments using an in-house-built point-collection-based spatially offset Raman spectroscopy (SORS) system were investigated to determine those critical to the three-dimensional (3D) positioning capability of SESORS. Here, we report the effects of the spatial offset magnitude and geometry on locating nanoparticles (NPs) mixed with silica powder as an imaging target through tissue and outline experimental techniques to allow for the correct interpretation of SESORS images to ascertain the correct location of NPs in the two-dimensional x, y-imaging plane at depth. More specifically, the effect of “linear offset-induced image drag” is presented, which refers to a spatial distortion in SESORS images caused by the magnitude and direction of the linear offset and highlight the need for an annular SORS collection geometry during imaging to neutralize these asymmetric effects. Additionally, building on these principles, the concept of “ratiometric SESORS imaging” is introduced for the location of buried inclusions in three dimensions. Together these principles are vital in developing a methodology for the location of surface-enhanced Raman scattering-active inclusions in three dimensions. This approach utilizes the relationship between the magnitude of the spatial offset, the probed depth, and ratiometric analysis of the NP and tissue Raman intensities to ultimately image and spatially discriminate between two distinct NP flavors buried at different depths within a 3D model for the first time. This research demonstrates how to accurately identify multiple objects at depth in tissue and their location using SESORS which addresses a key capability in moving SESORS closer to use in biomedical applications.

Nanoparticles and nanomaterials as inevitable modern toxic agents. Review. Part 2. Main areas of research on toxicity and techniques to measure a content of nanoparticles in tissues

The second part of the review considers the following three main areas of research on the toxicity of nanoparticles (NPs): environmental toxicity, molecular mechanisms of toxicity, and reproductive toxicity. The studies carried out on aquatic and soil model organisms are described, with consideration of the effects of NPs in concentrations close to natural in water with different salinity, as well as in comparison with the effects of ions. The articles devoted to various aspects of NP-induced oxidative stress are listed, the estimations of genotoxicity and mutagenicity of NPs using different standard methods are described, and the currently known data on the formation of protein crowns around NPs are considered. Questions are stated about the dose-dependence of effects and the influence of the applied stabilizing coating. The influence of NPs on the prenatal and postnatal development of various model vertebrate species is considered, which includes morphological disturbances, changes in gene expression and in the behavior of grown animals, as well as the influence on the reproductive system in adult females and males. The main methods for the quantitative measurements of the content of NPs in biological samples are also considered as the necessary stage of research on the toxicity of NPs for humans and animals.

Effects of cell permeability on distribution and penetration of drug into biological tissues: A multiscale approach

This article presents a finite volume heterogeneous multiscale method (FVHMM-p) to study drug delivery into biological tissues. The FVHMM-p accounts for the passive diffusion across the cell membrane, and the algorithm involves models at two scales: macroscale (tissue scale) and microscale (cell scale). The passive diffusion across membranes is treated in the microscale model which is apparently a three-compartment model; the first compartment involves solute diffusion in extracellular space, the second one includes diffusivity across the cell membrane, and the third one is meant for diffusion in the intracellular space. For the microscale model simulation, a permeable interface method based on central-type finite difference discretization is developed. This model is coupled with the tissue scale model to enforce the cellular (microscale) effects. Furthermore, the effects of cell membrane permeability and drug particle size on distribution and penetration of drug nanoparticles in tissues are investigated by conducting numerical experiments. The cell is considered to be elliptical, and the simulations with different configurations lead to the pronounced effects. The proposed model will be able to identify the optimal strategies in drug delivery.

In-Gel Assay to Evaluate Antioxidant Enzyme Response to Silver Nitrate and Silver Nanoparticles in Marine Bivalve Tissues

Silver is back in vogue today as this metal is used in the form of nanomaterials in numerous commercial products. We have developed in-gel electrophoretic techniques to measure the activity of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX), and used the same techniques in combination with HSP70 Western blot analysis to evaluate the effects of nanomolar amounts of silver nitrate and 5 nm alkane-coated silver nanoparticles in tissues of the marine bivalve Mytilus galloprovincialis (Lam.) exposed for 28 days in mesocosms. Our results showed a negligible effect for nanosilver exposure and dose-dependent effects for the nitrate form.

High-efficiency mechanically assisted alkaline extraction of nanoparticles from biological tissues for spICP-MS analysis.

The widespread use and increased exposure of nanoparticles call for technology to quantify their concentration and size distribution in biological matrices. As ex situ evaluation, facile extraction with high fidelity and efficiency is critical. In this work, single particle inductively coupled plasma mass spectrometry (spICP-MS) was used for nanoparticle number and distribution analysis, where a facile and highly efficient mechanically assisted alkaline digestion has been developed to extract nanoparticles at low alkali concentration. The optimization was performed using chicken tissues in vitro mixed with 30nm gold nanoparticles, mixture of 30nm and 60nm gold nanoparticles, and 45nm silver nanoparticles, respectively, which is, then, mechanically ground to form tissue homogenate and 2% TMAH is added. The nanoparticles are extracted with a recovery of more than 94% for all the spiked nanoparticle tissue samples. The extraction method has also been attempted to be applied to extract single-sized gold nanoparticles from various organs of mice mixed in vivo with the nanoparticles through intravenous injection, and led to consistent results with acid digestion. Mice injected intravenously with double-sized gold nanoparticle mixture were also studied, further showing that gold nanoparticles of 30nm and 60nm have no significant difference in their biodistribution in the same organ. To the best of our knowledge, this is the first attempt for multiple nanoparticles being extracted simultaneously and measured quantitatively from various organs, such as the heart, liver, spleen, lungs, and kidneys. We believe this method is beneficial to the safetyassessment and toxicokinetics studies for nanoparticles in tissues.

Differential responses of maize (Zea mays) at the physiological, biomolecular, and nutrient levels when cultivated in the presence of nano or bulk ZnO or CuO or Zn2+ or Cu2+ ions

Expanding applications of metal-based nanoparticles (NPs) in industry and agriculture have influenced agro-ecosystems. However, relatively little is known about the bioaccumulation, distribution, and phytotoxicity of ZnO-NPs, CuO-NPs, ZnO-bulk, CuO-bulk, Zn2+, or Cu2+ in maize. Plants were exposed to 0.05–2 mg ml−1 or g−1 of six tested materials in agar (7 days) in hydroponic medium (20 days), or sandy-clay-loam soil (20 or 40 days). Seed germination, emergence and lengths of plumules, principal and seminal roots were significantly inhibited by ZnO-NPs, CuO-NPs, Zn2+, and Cu2+. Toxicity was more pronounced in hydroponic culture than in soil, and perceptible alterations in biomolecules were evident. ICP-MS analysis exhibited progressive uptake of metals while morphological, elemental, and surface/deeper scanning showed translocation and distribution of NPs in tissues. Tested materials induced enhanced superoxide radical production, lipid peroxidation, and antioxidant enzymes and proline levels. Exposure significantly reduced P-accumulation, photosynthesis, and protein production. Zn2+ and Cu2+ were found to be more toxic than NPs. Compared to 20 days exposure in soil, toxicity slightly increased after 40 days. ZnO-NPs and CuO-NPs increased apoptotic sub-G1 population by 22.4% and 38%, respectively. These results provide a better understanding of the mechanistic aspects responsible for the nanotoxicities of ZnO- and CuO-NPs in maize.

3D Spatial Distribution of Nanoparticles in Mice Brain Metastases by X-ray Phase-Contrast Tomography.

Characterizing nanoparticles (NPs) distribution in multiple and complex metastases is of fundamental relevance for the development of radiological protocols based on NPs administration. In the literature, there have been advances in monitoring NPs in tissues. However, the lack of 3D information is still an issue. X-ray phase-contrast tomography (XPCT) is a 3D label-free, non-invasive and multi-scale approach allowing imaging anatomical details with high spatial and contrast resolutions. Here an XPCT qualitative study on NPs distribution in a mouse brain model of melanoma metastases injected with gadolinium-based NPs for theranostics is presented. For the first time, XPCT images show the NPs uptake at micrometer resolution over the full brain. Our results revealed a heterogeneous distribution of the NPs inside the melanoma metastases, bridging the gap in spatial resolution between magnetic resonance imaging and histology. Our findings demonstrated that XPCT is a reliable technique for NPs detection and can be considered as an emerging method for the study of NPs distribution in organs.

The possible role of vitamins E and C in reducing the toxicity of copper nanoparticles in the kidney and liver of the rats (Rattus norvegicus)

This study aims to ascertain the extent of accumulation of copper in the tissue of kidneys and liver, in addition to elucidate the effects of toxic nanoparticles on the kidneys and liver’s functions. Also it aims to measure some of the standards of antioxidants. We randomly had divided 56 rats (Rattus norvegicus) weigh 120 g ± 10 g into seven treatment groups and one of them is a controller. Rats in treatment groups were given 100 mg/kg/day of copper nanoparticles and 250 mg/kg/day of vitamins E and C.The obtained results had indicated an accumulation of copper nanoparticles in the liver and kidneys of the rats in the treatment groups. We also found that the accumulation in the liver is significantly more than in the kidneys. Treatment also resulted in the increase of ALT, AST and GGT enzymes level and serum urea and creatinine in blood serum in the copper nanoparticles treated groups. Also there’s increase in level of lipid peroxide and decrease in the level of glutathione in the liver and the kidneys. When we made a comparison between the controlled group with the treated groups by nanoparticle and vitamins, the results had confirmed the effective role of vitamins as antioxidants that reduce the accumulation of nanoparticles in tissues, and returns the level of liver enzymes, Kidney function, lipid peroxide and glutathione to almost normal levels.

Enhancing subcutaneous injection and target tissue accumulation of nanoparticles via co-administration with macropinocytosis inhibitory nanoparticles (MiNP).

A significant barrier to the application of nanoparticles for precision medicine is the mononuclear phagocyte system (MPS), a diverse population of phagocytic cells primarily located within the liver, spleen and lymph nodes. The majority of nanoparticles are indiscriminately cleared by the MPS via macropinocytosis before reaching their intended targets, resulting in side effects and decreased efficacy. Here, we demonstrate that the biodistribution and desired tissue accumulation of targeted nanoparticles can be significantly enhanced by co-injection with polymeric micelles containing the actin depolymerizing agent latrunculin A. These macropinocytosis inhibitory nanoparticles (MiNP) were found to selectively inhibit non-specific uptake of a second "effector" nanoparticle in vitro without impeding receptor-mediated endocytosis. In tumor bearing mice, co-injection with MiNP in a single multi-nanoparticle formulation significantly increased the accumulation of folate-receptor targeted nanoparticles within tumors. Furthermore, subcutaneous co-administration with MiNP allowed effector nanoparticles to achieve serum levels that rivaled a standard intravenous injection. This effect was only observed if the effector nanoparticles were injected within 24 h following MiNP administration, indicating a temporary avoidance of MPS cells. Co-injection with MiNP therefore allows reversible evasion of the MPS for targeted nanoparticles and presents a previously unexplored method of modulating and improving nanoparticle biodistribution following subcutaneous administration.

Hepatotoxicity study of nanotitania on Mice and Zebra fish: A comparison

The present paper for study aims the characterization and investigation of the oxidative stress induced toxicity of nanotitania in liver of mice and zebra fish models. Physical characterization for its size and the affirmation of phase by XRD, SEM, and TEM reveals, the particles as crystalline, predominant anatase phase with the mean size of about <50 nm. The toxic effect was assessed in vivo using the giant zebra fish 3-6 months old on two groups, viz, control and 24hr treated with 1ppm as experimental. Similarly 6-8 months old Mice with control and experimental groups (24 hour treatment of 50mg/kg bodyweight). Spectrophotometric analysis of the inductively coupled plasma optical emission confirmed the presence of nanoparticles in tissues. In both experimental models, a considerable raise in lipid peroxidation as well as liver marker enzymes ALT, AST and the decline within antioxidants such as SOD, Catalase, GPx due to TiO2 induced oxidant stress. Topographic evaluation of tissue through SEM reveals a remarkable uptake of nanotitania. Histopathological examination of TiO2 administrated groups infers cellular damage and DNA damage which was confirmed by COMET assay. It is substantial that nanoritania unlike to its bulk counterpart induces hepatotoxicity in both fish and Mice. The mice tissues are found to be more toxic than that of giant zebra fish in spite of better efficacy in its tissue.

Multiscale Analysis of Metal Oxide Nanoparticles in Tissue: Insights into Biodistribution and Biotransformation.

Metal oxide nanoparticles have emerged as exceptionally potent biomedical sensors and actuators due to their unique physicochemical features. Despite fascinating achievements, the current limited understanding of the molecular interplay between nanoparticles and the surrounding tissue remains a major obstacle in the rationalized development of nanomedicines, which is reflected in their poor clinical approval rate. This work reports on the nanoscopic characterization of inorganic nanoparticles in tissue by the example of complex metal oxide nanoparticle hybrids consisting of crystalline cerium oxide and the biodegradable ceramic bioglass. A validated analytical method based on semiquantitative X‐ray fluorescence and inductively coupled plasma spectrometry is used to assess nanoparticle biodistribution following intravenous and topical application. Then, a correlative multiscale analytical cascade based on a combination of microscopy and spectroscopy techniques shows that the topically applied hybrid nanoparticles remain at the initial site and are preferentially taken up into macrophages, form apatite on their surface, and lead to increased accumulation of lipids in their surroundings. Taken together, this work displays how modern analytical techniques can be harnessed to gain unprecedented insights into the biodistribution and biotransformation of complex inorganic nanoparticles. Such nanoscopic characterization is imperative for the rationalized engineering of safe and efficacious nanoparticle‐based systems.

Neutron activation analysis as a tool for tracing the accumulation of silver nanoparticles in tissues of female mice and their offspring

The silver accumulation in different tissues of female mice and their offspring after prolonged oral administration of silver nanoparticles to the females during pregnancy and lactation was investigated. Silver content in different organs (blood, liver, brain, kidney and lungs) was determined by means of neutron activation analysis. According to the obtained data silver nanoparticles are able to reach and cross the placental barrier and blood-to-brain barrier in both mice female and their offspring. In mice female the highest silver concentration was determined in lungs, followed by brain, liver, kidney and blood. In offspring silver bioaccumulation changed in the following order lungs > brain > blood > liver > kidney. The average specific mass content of silver which crossed the blood–brain barrier was 373 ± 75 ng (for female) and 385 ± 57 ng (for offspring). The obtained results are important for studies in developmental and reproductive toxicity of nanomaterials.