Nanoparticles In Organs Research Articles

Non-linear photonics for intravital microscopy in health sciences: application to detection of nanoparticles in organs

Intravital microscopy (IM) for health sciences can be achieved by means of Laser Scanning Microscopy (LSM) in two Photon (2P) excitation conditions using Infrared (IR) illumination which has good penetration in all tissues and organs. Imaging is then performed using 2P emission of fluorescence (2PE) and second harmonic generation (SHG) modes which provide high contrast and good spatial resolution. These modes do reveal the different parts of organs due to differential fluorescence and SHG. In the case of atherotic aorta, for instance, the formation of the atherotic plaque can be visualised and located with respect of aorta's structure: an important application is the diagnosis about unstability or stability of the plaque. Also the spatial resolution of LSM allows revealing the heterogeneous biodistribution of iron oxide core (USPIO) nanoparticles for diagnosis of the atherotic plaque, from the aorta's scale down to the subcellular level: detection of aggregates of USPIOs at the subcellular level supports the model of USPIOs phagocytised by macrophages which target the plaque.

In vivo analysis of the size- and time-dependent uptake of NaYF4:Yb,Er upconversion nanocrystals by pumpkin seedlings.

We have investigated the kinetics of the uptake and the translocation of nanoparticles in plants. Nearly monodisperse NaYF4:Yb,Er nanocrystals were used, either spherical particles with a diameter of 14 nm or nanorods with a length of 41 nm and a diameter of 22 nm. After watering pumpkin seedlings (Cucurbita maxima) with aqueous colloidal solutions of the particles, intact nanocrystals in the plants were detected in vivo by exciting their upconversion luminescence with a near infrared laser diode (978 nm). The particle concentration in different plant parts was determined by X-ray fluorescence spectroscopy (XRF), making use of the high sensitivity of Yttrium in XRF measurements and its low natural abundance in plants. The results show a fast uptake and translocation of the nanoparticles in all plant organs within three hours. The smaller particles move in the plants faster than the larger ones.

Establishment of a trimodality analytical platform for tracing, imaging and quantification of gold nanoparticles in animals by radiotracer techniques.

This study aims to establish a (198)Au-radiotracer technique for in vivo tracing, rapid quantification, and ex vivo visualization of PEGylated gold nanoparticles (GNPs) in animals, organs and tissue dissections. The advantages of GNPs lie in its superior optical property, biocompatibility and versatile conjugation chemistry, which are promising to develop diagnostic probes and drug delivery systems. (198)Au is used as a radiotracer because it simultaneously emits beta and gamma radiations with proper energy and half-life; therefore, (198)Au can be used for bioanalytical purposes. The (198)Au-tagged radioactive gold nanoparticles ((198)Au-GNPs) were prepared simply by irradiating the GNPs in a nuclear reactor through the (197)Au(n,γ)(198)Au reaction and subsequently the (198)Au-GNPs were subjected to surface modification with polyethylene glycol to form PEGylated (198)Au-GNPs. The (198)Au-GNPs retained physicochemical properties that were the same as those of GNP before neutron irradiation. Pharmacokinetic and biodisposition studies were performed by intravenously injecting three types of (198)Au-GNPs with or without PEGylation into mice; the γ radiation in blood specimens and dissected organs was then measured. The (198)Au-radiotracer technique enables rapid quantification freed from tedious sample preparation and shows more than 95% recovery of injected GNPs. Clinical gamma scintigraphy was proved feasible to explore spatial- and temporal-resolved biodisposition of (198)Au-GNPs in living animals. Moreover, autoradiography, which recorded beta particles from (198)Au, enabled visualizing the heterogeneous biodisposition of (198)Au-GNPs in different microenvironments and tissues. In this study, the (198)Au-radiotracer technique facilitated creating a trimodality analytical platform for tracing, quantifying and imaging GNPs in animals.

Bioaccumulation of silver and gold nanoparticles in organs and tissues of rats studied by neutron activation analysis

Bioaccumulation of silver (Ag) and gold (Au) nanoparticles (NPs) with mean sizes of 6 nm and 35 nm, respectively, has been studied after their intragastric administration to rats at a dose of 100 μg/kg of body weight for 28 or 14 days. The organs and tissues (liver, kidney, spleen, heart, gonads brain, and blood) were subjected to thermal neutron activation, and, then, the activity of the 110mAg and 198Au isotopes generated was measured. The NPs of both metals were detected in all biological samples studied, the highest specific weight and content of Ag NP being found in the liver, and those of Au being found in kidneys of animals. The content of Ag NPs detected in the brain was 66.4 ± 5.6 ng (36 ng/g tissue), no more than 7% ofthese NPs being localized in the lumen of brain blood vessels. The content of Ag and Au NPs found in organs and tissues of rats could be regarded as nonhazardous (nontoxic) in accordance with the known literature data.

Simulation of the Motion of Magnetic Nanoparticles in Human Tissues

In this paper an attempt on the basis of the theory of mobile cellular automata to develop a model of motion of magnetic nanoparticles in human organs and tissues. In the framework of the method of movable cellular automata, the simulated system (tissues and organs) is represented by an assembly of interacting automata (elements of finite size). The concept of the method is based on the introduction of a new state type – the state of a pair of automata. Setting various parameters of the medium (tissues and organs). We can vary behavior of these particles in these mediums.

Formation of certified reference materials and standard measurement guides for development of traceable measurements of mass fractions and sizes of nanoparticles in different media and biological matrixes on the basis of gamma-ray and optical spectroscopy

Metrological assurance has been developed and formed for a promising technique for measuring the mass fraction and number concentration of nanoparticles containing silver or zinc in different media, including those of a biological nature, i.e., the gamma-ray spectroscopy of neutron-activated samples along with dynamic light scattering. The advantage of this complex measurement technique over other approaches to analytically controlling nanomaterials is discussed. The certified reference materials and standard guides developed in order to ensure the uniformity and traceability of measurements are described. The technique is tested in experiments on the kinetics of accumulation and removal of silver nanoparticles in different organs and excrement of laboratory rats.

Distribution of c-erbB2 Antisense Probe Labeled with Superparamagnetic Iron Oxide Nanoparticles in the Major Organs of Mice on MR Imaging

Background: The aim of this study was to investigate the distribution of the c-erbB2 antisense probe labeled with superparamagnetic iron oxide nanoparticles in the major organs of mice by MR imaging. Methods: Sixty BALB/c mice were randomly divided into experimental and control groups. MR scans were performed in each mouse of the experimental group at five different time points (10, 30, 60, 180 and 360 min) after injection of the antisense probe. The signal from each major organ (liver, spleen, heart, kidney and muscle tissue) in comparison with the background signal (signal to noise ratio) was determined at each time point as a measure of the distribution of the antisense probe. Six control mice were killed at each of the same time points and the organs immediately removed for determination of their iron content. Results: After injection of the antisense probe, the highest enrichment of the probe was seen in the spleen, reaching a peak at 180 min, followed by the liver, muscle, heart and kidney. Conclusions: MR imaging can visualize the distribution of c-erbB2 antisense probe labeled with superparamagnetic iron oxide nanoparticles in the major organs of mice, and this may provide the basis for further in vivo studies of MR imaging time and dose selection.

The Technique of Enhancing the Transdermal Penetration for the Gold Nanoparticles and Perspectives of Application

Background: In recent years, worldwide attention of researchers focused on the practical implementation of nanoscale materials in biomedical technology. It’s proved that intravenous injected gold nanoparticles are accumulated in tumor tissues. However, when gold nanoparticles injected intravenously negative effects in the internal organs of experimental animals are observed. 160 nm diameter particles affect the wall of blood vessels, resulting in vacuolar degeneration of endothelial cells. Particles with a diameter of 50 nm lead to more expressed changes in the internal organs. Injection of the particles diameter of 15 nm causes moderate degeneration of parenchymal cells of internal organs and circulatory disorders. Materials and Methods: In current research, for the first time using the methods of experimental pathology the permeability of intact and damaged skin for nanoscale gold particles in combination with organosulfur compounds—imethylsulfoxide and tiofansulfoxide were studied. We used 140 male outbred white rats with an average weight 150 - 200 grams. All the animals were divided into one control and three experimental groups. Results: Laser microperforation skin with ultrasound treatment can provide good skin permeability, but in contrast to use of agents with organosulfur compounds inflammatory reaction, the destruction of superficial and deep skin tissue structural elements are observed. The comparative efficacy of dimethylsulfoxide and tiofansulfoxide for transdermal permeability of gold nanoparticles was studied. It’s proved that in topical application solution of nanoparticles with organosulfur compounds negative effects of the accumulation of nanoparticles in the internal organs, disorders of organ and tissue microcirculation, development in the degenerative changes are not observed. We found that the depth of penetration of damaged skin (contact dermatitis) for the gold nanoparticles in combination with organosulfur compounds, and ultrasound exposure is substantially higher than the penetration of intact skin.

Long-Term Biodistribution and Biocompatibility Investigation of Dextran-Coated Magnetite Nanoparticle Using Mice as the Animal Model

Magnetic resonance is used to investigate biodistribution aspects of dextran-coated magnetite nanoparticles (9.4 nm core diameter) in both liver and spleen from 5 minutes up to 6 months after intravenous administration of a magnetic fluid sample in female Swiss mice. Using magnetic resonance data important parameters such as the absorption half-life (t 1/2 = 12 +/- 2 min in the liver and t 1/2 = 11 +/- 2 min in the spleen), the peak time (1.7 +/- 0.2 h in the liver and 1.9 +/- 0.2 h in the spleen), and the disposition half-life of the dextran-coated magnetite nanoparticles in mice organs (t 1/2 = 70 +/- 10 h in the liver and t 1/2 = 32 +/- 7 h in the spleen) were assessed. In addition, light and electron microscopy showed several aspects that may be related to the iron metabolism. Microscopic analysis also revealed that although magnetite nanoparticles or iron released from them are retained in the organism for a long period of time, no morphologic alteration is induced by the intravenous administration of the magnetic fluid sample, evidencing its biocompatibility. The used tests may represent an adequate methodology for nanotoxicology evaluation.

NIR-labeled perfluoropolyether nanoemulsions for drug delivery and imaging

Theranostic nanoparticle development recently took center stage in the field of drug delivery nanoreagent design. Theranostic nanoparticles combine therapeutic delivery systems (liposomes, micelles, nanoemulsions, etc.) with imaging reagents (MRI, optical, PET, CT). This combination allows for non-invasive in vivo monitoring of therapeutic nanoparticles in diseased organs and tissues. Here, we report a novel perfluoropolyether (PFPE) nanoemulsion with a water-insoluble lipophilic drug. The formulation enables non-invasive monitoring of nanoemulsion biodistribution using two imaging modalities, 19F MRI and near-infrared (NIR) optical imaging. The nanoemulsion is composed of PFPE-tyramide as a 19F MRI tracer, hydrocarbon oil, surfactants, and a NIR dye. Preparation utilizes a combination of self-assembly and high energy emulsification methods, resulting in droplets with average diameter 180nm and low polydispersity index (PDI less than 0.2). A model nonsteroidal anti-inflammatory drug (NSAID), celecoxib, was incorporated into the formulation at 0.2mg/mL. The reported nanoemulsion's properties, including small particle size, visibility under 19F NMR and NIR fluorescence spectroscopy, and the ability to carry drugs make it an attractive potential theranostic agent for cancer imaging and treatment.

Pharmacokinetics, tissue distribution, and excretion of zinc oxide nanoparticles

BackgroundThis study explored the pharmacokinetics, tissue distribution, and excretion profile of zinc oxide (ZnO) nanoparticles with respect to their particle size in rats.MethodsTwo ZnO nanoparticles of different size (20 nm and 70 nm) were orally administered to male and female rats, respectively. The area under the plasma concentration-time curve, tissue distribution, excretion, and the fate of the nanoparticles in organs were analyzed.ResultsThe plasma zinc concentration of both sizes of ZnO nanoparticles increased during the 24 hours after administration in a dose-dependent manner. They were mainly distributed to organs such as the liver, lung, and kidney within 72 hours without any significant difference being found according to particle size or rat gender. Elimination kinetics showed that a small amount of ZnO nanoparticles was excreted via the urine, while most of nanoparticles were excreted via the feces. Transmission electron microscopy and x-ray absorption spectroscopy studies in the tissues showed no noticeable ZnO nanoparticles, while new Zn-S bonds were observed in tissues.ConclusionZnO nanoparticles of different size were not easily absorbed into the bloodstream via the gastrointestinal tract after a single oral dose. The liver, lung, and kidney could be possible target organs for accumulation and toxicity of ZnO nanoparticles was independent of particle size or gender. ZnO nanoparticles appear to be absorbed in the organs in an ionic form rather than in a particulate form due to newly formed Zn-S bonds. The nanoparticles were mainly excreted via the feces, and smaller particles were cleared more rapidly than the larger ones. ZnO nanoparticles at a concentration below 300 mg/kg were distributed in tissues and excreted within 24 hours. These findings provide crucial information on possible acute and chronic toxicity of ZnO nanoparticles in potential target organs.

The Influence of Size and Exposure Duration of Gold Nanoparticles on Gold Nanoparticles Levels in Several Rat Organs In vivo

Background: The bioaccumulation and toxicity of Gold Nanoparticles (GNPs) in several organs of rats becomes of more necessity prior to using them in drug delivery, diagnostics, and treatment. The GNPs levels in several rat organs in vivo have not been previously documented. This study was aimed to evaluate the influence of size and exposure duration of GNPs on the GNPs levels in several organs of rats in vivo. Methods: Thirty rats were divided into a control group (NG: n = 10), group 1 (G1A: infusion of 10 nm GNPs for 3 days; n = 5; G1B: 10 nm GNPs for 7 days; n = 5) and group 2 (G2A: 50 nm GNPs for 3 days; n = 5; G2B: 50 nm GNPs for 7 days; n = 5). 50 μl of GNPs dissolved in aqueous solution were administered intraperitoneally every day for 3 and 7 days. Results: The GNPs levels were evaluated in several rat organs by Inductively Coupled Plasma-Mass Spectroscopy (ICP-MS) and Atomic Absorption Spectroscopy (AAS). In comparison with the control group, the GNPs levels increased in all the examined organs with G1A, G1B, G2A and G2B. The highest percentage normalized increase in the liver and lung organs were 468.6% and 273.4%, respectively with 10 nm GNPs after administration period of 7 days. The highest percentage normalized increase in the kidney and heart organs were 258.7% and 242.6%, respectively with 10 nm GNPs for administration period of 3 days. Conclusions: Our results might indicate that GNPs are mostly taken up and accumulate in organs, suggesting the toxic effects induced by the smaller GNPs. These conclusions are further supported by histological investigation suggesting that the highest toxic effects were induced by the smaller GNPs and related to the time exposure of GNPs.

Development and validation of a simple reversed-phase HPLC method for the determination of camptothecin in animal organs following administration in solid lipid nanoparticles

A simple, sensitive and specific high-performance liquid chromatography (HPLC) assay for the quantification of camptothecin (CPT), a potent anticancer candidate, incorporated into solid lipid nanoparticles (SLN) in several rat organs (brain, heart, kidneys liver, lung, spleen) and serum was developed and validated. The sample pre-treatment involved organs homogenisation followed by CPT extraction. The samples were injected onto an analytical reversed-phase (RP) Mediterranea™ Sea18 column maintained at 30°C. The chromatographic separation was achieved by gradient elution consisting of triethyamine buffer pH 5.5 and acetonitrile at a flow rate of 1.2mL/min in 16min of run time and retention time of 9.8min (lactone). Fluorescence detection was used at the excitation and emission of 360 and 440nm, respectively. The calibration curves in the different organs, serum and in PB3 were linear (r2>0.9999) over CPT concentrations ranging from 1 to 200ng/mL or 0.5 to 200ng/mL (n=6), respectively. The method was shown to be specific, accurate (between 94.4±4.5% and 108.9±0.6%) and precise at the intra-day and inter-day levels as reflected by the coefficient of variation (CV<6.3%) at three different concentrations (10, 50 and 100ng/mL) in all matrices. Stability studies showed that CPT was stable in all matrices after 24h of incubation at room temperature (RT), after 24h in the autosampler or after three freeze/thaw cycles. The mean recoveries of CPT in suspension, loaded into SLN and in a physical mixture with SLN at three concentrations of 10, 50 and 200ng/mL were higher than 86.4%. The detection limit (DL) was ≤0.2ng/mL and the quantification limit (QL) was ≤0.5ng/mL. The method developed is reliable, precise and accurate and can be used in the determination of CPT amount in rat organ samples after i.v. administration of CPT in suspension, in physical mixture with SLN and incorporated in SLN.

Detection of the Presence of Gold Nanoparticles in Organs by Transmission Electron Microscopy.

Gold nanoparticles of 10 nm and 250 nm were intravenously injected in rats. At 24 h after administration, tissues were collected and prepared for transmission electron microscopy (TEM). In the liver and spleen of animals treated with 10 nm gold nanoparticles, groups of nanoparticles were observed that could be positively identified by Energy Dispersive X-ray (EDX) analysis to contain gold, while nanoparticles could not be detected in the heart, kidney and brain. The 10 nm gold nanoparticles were present in the phagocytic cells of the reticulo-endothelial system (RES). The 250 nm gold nanoparticles could not be detected in any of the organs investigated. Considering the number of 250 nm gold nanoparticles administered, calculations showed that it would indeed be almost impossible to detect the 250 nm gold nanoparticles in TEM preparations in view of the very low number of particles that would be theoretically present in one TEM tissue section. This shows that relatively high numbers of nanoparticles need to be administered to enable the detection of nanoparticles in organs by TEM. In a number of samples, several globular structures of approximately the expected size were found in liver cells and the endothelium of blood vessels in the brain. However, elemental analysis with EDX detection showed that these structures did not contain gold. Our studies thus indicate that the in vivo identification of nanoparticles cannot only depend on the detection of nanosized structures in cells. An additional identification of the composing elements of the nanomaterial is necessary for a positive identification of the nanomaterial.

Anti-oxidant effect of gold nanoparticles restrains hyperglycemic conditions in diabetic mice

BackgroundOxidative stress is imperative for its morbidity towards diabetic complications, where abnormal metabolic milieu as a result of hyperglycemia, leads to the onset of several complications. A biological antioxidant capable of inhibiting oxidative stress mediated diabetic progressions; during hyperglycemia is still the need of the era. The current study was performed to study the effect of biologically synthesized gold nanoparticles (AuNPs) to control the hyperglycemic conditions in streptozotocin induced diabetic mice.ResultsThe profound control of AuNPs over the anti oxidant enzymes such as GSH, SOD, Catalase and GPx in diabetic mice to normal, by inhibition of lipid peroxidation and ROS generation during hyperglycemia evidence their anti-oxidant effect during hyperglycemia. The AuNPs exhibited an insistent control over the blood glucose level, lipids and serum biochemical profiles in diabetic mice near to the control mice provokes their effective role in controlling and increasing the organ functions for better utilization of blood glucose. Histopathological and hematological studies revealed the non-toxic and protective effect of the gold nanoparticles over the vital organs when administered at dosage of 2.5 mg/kilogram.body.weight/day. ICP-MS analysis revealed the biodistribution of gold nanoparticles in the vital organs showing accumulation of AuNPs in the spleen comparatively greater than other organs.ConclusionThe results obtained disclose the effectual role of AuNPs as an anti-oxidative agent, by inhibiting the formation of ROS, scavenging free radicals; thus increasing the anti-oxidant defense enzymes and creating a sustained control over hyperglycemic conditions which consequently evoke the potential of AuNPs as an economic therapeutic remedy in diabetic treatments and its complications.

Investigation of biodistribution of gold nanoparticles in healthy animals

The goal of this work is to investigate the peculiarities of biodistribution and the effects of gold nanoparticles in different organs and tissues of animals after intravenous administration. Nanoparticles are shown to produce neither acute nor long-term pathomorphologic alterations in the organs of healthy mice. Using transmission electron microscopy, a significant number of nanoparticles were detected in blood and urine 4 h after administration. Gold nanoparticles are shown to accumulate primarily in the spleen and kidneys, with a peak accumulation being reached on day 7 after injection. Single nanoparticles are detected in the brain, heart, and liver.

Toxicity of Tungsten Carbide and Cobalt-Doped Tungsten Carbide Nanoparticles in Mammalian Cells in Vitro

BackgroundTungsten carbide nanoparticles are being explored for their use in the manufacture of hard metals. To develop nanoparticles for broad applications, potential risks to human health and the environment should be evaluated and taken into consideration.ObjectiveWe aimed to assess the toxicity of well-characterized tungsten carbide (WC) and cobaltdoped tungsten carbide (WC-Co) nanoparticle suspensions in an array of mammalian cells.MethodsWe examined acute toxicity of WC and of WC-Co (10% weight content Co) nanoparticles in different human cell lines (lung, skin, and colon) as well as in rat neuronal and glial cells (i.e., primary neuronal and astroglial cultures and the oligodendro cyte precursor cell line OLN-93). Furthermore, using electron microscopy, we assessed whether nanoparticles can be taken up by living cells. We chose these in vitro systems in order to evaluate for potential toxicity of the nanoparticles in different mammalian organs (i.e., lung, skin, intestine, and brain).ResultsChemical–physical characterization confirmed that WC as well as WC-Co nanoparticles with a mean particle size of 145 nm form stable suspensions in serum-containing cell culture media. WC nanoparticles were not acutely toxic to the studied cell lines. However, cytotoxicity became apparent when particles were doped with Co. The most sensitive were astrocytes and colon epithelial cells. Cytotoxicity of WC-Co nanoparticles was higher than expected based on the ionic Co content of the particles. Analysis by electron microscopy demonstrated presence of WC nanoparticles within mammalian cells.ConclusionsOur findings demonstrate that doping of WC nanoparticles with Co markedly increases their cytotoxic effect and that the presence of WC-Co in particulate form is essential to elicit this combinatorial effect.

Quantitative detection of engineered nanoparticles in tissues and organs: An investigation of efficacy and linear dynamic ranges using ICP-AES

The absence of effective non-isotopic quantification methods to determine in vivo nanoparticle kinetics and distribution is a key obstacle to the development of various biomedical nanotechnologies. This paper presents a novel adaptation of the established technology of Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES) to a simple technique intended to address this obstacle. Applicability to three varieties of nanoparticles, (CdSe/ZnS quantum dots (QD), gold nanoparticles, and Fe3O4 nanoparticles) was investigated, and particle detection sensitivity was shown in moles of particles per gram of tissue. Using gold nanoparticles, increased particle size corresponded with lower molar detection thresholds. Minimum linear detection ranges of 2.5 orders of magnitude for QDs and 1.5 orders of magnitude for all three sizes of gold were demonstrated. The detection of the Fe3O4 particles was hampered by the natural presence of Fe2+ in tissues, showing that the technique is not suitable for measuring nanoparticles composed of endogenous elements. These detection levels and ranges demonstrate that this technique is useful for quantifying nanoparticles in excised organs, after in vivo dosing.

Sub-cellular accumulation of magnetic nanoparticles in breast tumors and metastases

In this study, the sub-cellular accumulation of superparamagnetic iron oxide nanoparticles (SPIONs) in breast tumors and peripheral organs were investigated. MNPs were conjugated with luteinizing hormone releasing hormone (LHRH), whose receptors are expressed by most types of breast cancer cells. After the nanoparticles were injected into female nude mice bearing MDA-MB-435S.luc tumors, the mice were sacrificed to collect tumors and peripheral organs for biological and TEM analyses. LHRH conjugated SPIONs (LHRH- SPIONs) were found to accumulate in cancer cells, mainly in the primary tumors and the metastatic lungs, where they aggregated to form clusters. In contrast, most of the unconjugated SPIONs were collected in the liver cells. The results suggest that LHRH- SPIONs can be used to target cancer cells in the primary breast tumors and the lung metastases. TEM is also shown to be a useful tool for the studies of sub-cellular distributions of SPIONs in tumors and tissues.

Cells Involved in the Capture of Nanoparticles in Hematopoietic Organs

The affinity of nanoparticles for hematopoietic organs could be valuable for the targeting of certain stimulating factors to those tissues, but this affinity should also be taken into account in the toxicological evaluation of those carriers, especially when they are loaded with antimitotic compounds such as doxorubicin. However, the cells responsible for the capture of the nanoparticles and their localization in these organs is an important point to know before trying to modulate the nanoparticle's tissue distribution. Thus, we have studied, in this paper, the capture, the localization, and the retention in the bone marrow and in the spleen of biodegradable poly(isohexyl cyanoacrylate) nanoparticles as well as of nonbiodegradable polystyrene nanoparticles. The histological localization of these nanoparticles has been completed by cytological localization with a method used in cytochemistry for the evaluation of intracellular accumulation of various substances, such as iron deposits in bone marrow sideroblasts. These data indicate that, in the bone marrow, after a quick passage through the endothelium, nanoparticles were dispersed throughout in the tissue and captured by all types of phagocytizing cells. In the spleen, nanoparticles were mainly localized in large angular capturing cells in the marginal zone of the lymphoid follicles.