Nanoparticles In Liver Research Articles

Hepatic-targeted delivery of astaxanthin for enhanced scavenging free radical scavenge and preventing mitochondrial depolarization

Astaxanthin (AST), as natural hydrophobic nutrition, has exhibited health-promoting benefits for its outstanding antioxidant property. However, most studies tend to enhance its stability and solubility while the targeted delivery of AST is limited. In this study, liver-targeted nanocarriers were designed and prepared by lactobionic acid-modified (2-hydroxypropyl-β-cyclodextrin) for efficient controlled delivery of AST. The minimum average size of AST nanoparticles was about 98 nm with a polydispersity index (PDI) of 0.41. The lactobionic acid-modified AST nanoparticles exhibited significant cellular uptake, and an admirable ability to scavenge free radicals for H2O2-induced HepaRG cells in preventing mitochondrial depolarization. Moreover, accumulation of AST nanoparticles in liver was observed due to the modification of lactobionic acid (LA) of the nanocarriers through the specific binding of LA-asialoglycoprotein receptors. The results in this study provided a new idea for liver-specific nutrition delivery of AST in developing functional food for liver disease nutrition intervention.

Fabrication and Pulse Sequences Evaluation of Iron Oxides Nanoparticles as MRI Contrast Agent

The objective of this in vivo study is to enhance the T2-weighted MRI contrast using superparamagnetic nanoparticles in liver and spleen of rabbits for biomedicine application. Superparamagnetic nanoparticles were synthesized using co-precipitation method. Superparamagnetic nanoparticles were characterized using SEM, EDX, VSM, magnetic resonance relaxation and magnetic resonance imaging (MRI). T1 and T2 relaxations were measured as function of concentration of contrast agents in liver and spleen. High relaxivity ratio r2/r1 showed the efficacy of prepared T2- weighted MRI contrast agent. Rabbits were anesthetized using xylazine and ketamine salts for medical procedure. Ketamine and xylazine were injected with the dose rate of ketamine 25-40 mg/kg and xylazine 2.5-5mg/kg intra-muscularly for veterinary anesthesia. MRI of albino rabbits was executed at 0.35 Tesla using magnetic nanoparticles. FDA approved, 0.2 ml/kg dose of contrast agents was injected in rabbits for MRI scanning. MRI axial and coronal, T1-W and T2-W images of liver and spleen were taken using Spin Echo (SE) at TE=92 and TR=551 and STIR at TE=24 and TR=5170. Spin software was used to estimate the intensity of signal in region of interest induced by magnetic contrast agent. In vivo, MRI study of magnetic contrast agents demonstrated the high T2 -weighted contrast on MRI images of liver and spleen of rabbits. This research also concludes that superparamagnetic nanoparticles may be used as MRI contrast agents for biomedicine application to see the pathology of living organs even at low tesla field.

Proteomics reveals multiple effects of titanium dioxide and silver nanoparticles in the metabolism of turbot, Scophthalmus maximus

Titanium dioxide (TiO2) and silver (Ag) NPs are among the most used engineered inorganic nanoparticles (NPs); however, their potential effects to marine demersal fish species, are not fully understood. Therefore, this study aimed to assess the proteomic alterations induced by sub-lethal concentrations citrate-coated 25 nm (“P25”) TiO2 or polyvinylpyrrolidone (PVP) coated 15 nm Ag NPs to turbot, Scophthalmus maximus. Juvenile fish were exposed to the NPs through daily feeding for 14 days. The tested concentrations were 0, 0.75 or 1.5 mg of each NPs per kg of fish per day. The determination of NPs, Titanium and Ag levels (sp-ICP-MS/ICP-MS) and histological alterations (Transmission Electron Microscopy) supported proteomic analysis performed in the liver and kidney. Proteomic sample preparation procedure (SP3) was followed by LC-MS/MS. Label-free MS quantification methods were employed to assess differences in protein expression. Functional analysis was performed using STRING web-tool. KEGG Gene Ontology suggested terms were discussed and potential biomarkers of exposure were proposed. Overall, data shows that liver accumulated more elements than kidney, presented more histological alterations (lipid droplets counts and size) and proteomic alterations. The Differentially Expressed Proteins (DEPs) were higher in Ag NPs trial. The functional analysis revealed that both NPs caused enrichment of proteins related to generic processes (metabolic pathways). Ag NPs also affected protein synthesis and nucleic acid transcription, among other processes. Proteins related to thyroid hormone transport (Serpina7) and calcium ion binding (FAT2) were suggested as biomarkers of TiO2 NPs in liver. For Ag NPs, in kidney (and at a lower degree in liver) proteins related with metabolic activity, metabolism of exogenous substances and oxidative stress (e.g.: NADH dehydrogenase and Cytochrome P450) were suggested as potential biomarkers. Data suggests adverse effects in turbot after medium/long-term exposures and the need for additional studies to validate specific biological applications of these NPs.

The potential protective role of apigenin against oxidative damage induced by nickel oxide nanoparticles in liver and kidney of male Wistar rat, Rattus norvegicus.

Nickel oxide nanoparticles (NiONPs) are involved in several applications but still have some adverse effects. Apigenin (APG) is a widespread natural product with antioxidative, anticancer, and anti-inflammatory properties. The present work aimed to study the protective role of APG against the NiONP-induced toxicity in male Wistar rats. Rats were randomly distributed to one control group and three treated groups. The treated groups were orally administered NiONPs (100mg/kg) alone, APG (25mg/kg) alone, or APG 1h before NiONPs, once daily for 28days. Blood, liver, and kidney were collected after 7, 14, and 28days of administration for Ni accumulation, hematological, biochemical, histological, and transmission electron microscopy (TEM) investigations. As compared to the controls, the administration of NiONPs alone significantly elevated the levels of Ni, malondialdehyde, total cholesterol, low-density lipoprotein cholesterol, creatinine, urea, blood urea nitrogen, and the activity of alanine and aspartate aminotransferases as well as the count of white blood cells. Besides, marked reductions in the activity of superoxide dismutase, and the levels of glutathione, high-density lipoprotein cholesterol, total proteins, albumin, globulin, hemoglobin, packed cell volume, and red blood cell count were reported. Histologically, the liver and kidney of rats administered NiONPs alone showed remarkable disturbances. According to TEM, subcellular alterations were observed in the liver and kidney of rats administered NiONPs alone. In contrast, APG administering before NiONPs substantially alleviated all the studied parameters. In conclusion, APG can ameliorate the NiONP-induced hepatotoxicity and nephrotoxicity in male Wistar rats.

PREPARATION AND EVALUATION OF SURFACE MODIFIED NANOPARTICLES OF CALCIUM PHOSPHATE AS EXTRACT CARRIER

Objective: The aim of this study was to develop, optimize and characterize carbohydrate coated calcium phosphate nanoparticles of Chelidonium majus L. extract along with carried out in vivo study to observe activity in the liver.
 Methods: Surface modified calcium phosphate nanoparticles of Chelidonium majus L. extract were developed and optimized. Extract loading and particle size were the two responses, effects on which were analyzed. Characterization studies, in vitro extract release and in vivo distribution studies were carried out. Also in vivo histopathological analysis was carried out to observe effects of extract loaded nanoparticles in liver of wistar albino rats in paracetamol, rifampicin-isoniazid, cisplatin and carbon tetrachloride-induced hepatotoxicity.
 Results: Pareto chart and surface response curve indicated that sonication time, the concentration of lactose and concentration of extract were important factors affecting particle size and extract loading. ANOVA was performed and obtained data pointed out that model was significant for both responses. Particle size and zeta potential results indicated the stability of prepared nanoparticles along with extract was loaded (37.22 %) satisfactorily on coated cores. Characterization studies indicated no interaction between the components and also extract release demonstrated diffusion-controlled mechanism. These extract loaded nanoparticles were largely found in the liver than heart, lungs. Hepatoprotective activity of nanoparticles of the extract was confirmed by correlating histopathology results of normal, toxic, silymarin treated, extract-treated and formulation treated groups.
 Conclusion: Lactose coated nanoparticles of calcium phosphate proved to be excellent carriers of plant extract. These nanoparticles efficiently targeted liver and generated cellular protective action in hepatic damage.

Deciphering the particle specific effects on metabolism in rat liver and plasma from ZnO nanoparticles versus ionic Zn exposure

Toxicity of ZnO nanoparticles (NPs) are often related to the release of Zn2+ ions due to their dissolution. Studies also suggest that the toxicity of ZnO NPs cannot be solely explained by the release of Zn2+ ions; however, there is a lack of direct evidence of ZnO particulate effects. This study compared the acute toxicity of ZnO NPs and ZnSO4 following intranasal exposure using a combination of metallomics and metabolomics approaches. Significant accumulation of Zn in the liver was only found in the ZnO NP treatment, with 29% of the newly accumulated Zn in the form of ZnO as revealed by X-ray fine structure spectroscopy (XAFS). This is the first direct evidence suggesting the persistence of ZnO NPs in liver upon intranasal exposure. Although both ZnO NPs and ZnSO4 altered the metabolite profiles, with some overlaps and considerable specificity, of both liver and plasma samples, more and distinct metabolites in the liver and opposite effects in the plasma were altered by ZnO NPs compared with ZnSO4, consistent with no accumulation of Zn detected in liver from ZnSO4. Specifically, a large number of antioxidant-related compounds and energetic substrates were exclusively elevated in the liver of ZnO NP-treated animals. These findings provided direct evidence that persistence of ZnO NPs induced particle-specific effects on the antioxidant systems and energy metabolism pathways.

Particle Background Levels In Human Tissues—PABALIHT project. Part I: a nanometallomic study of metal-based micro- and nanoparticles in liver and kidney in an Italian population group

We used field-emission scanning electron microscopy (FESEM) coupled with energy dispersive X-ray spectroscopy (EDS) microanalysis to determine size, shape, and elemental composition of particles in the liver and kidney autopsy of 35 subjects living in Sardinia. Particles were detected in 94% of livers and in 97% of kidney samples as aggregates, ranging between 50 nm and 100 μm. A total of 513 particle aggregates were observed in all tissues (276 in the liver and 237 in the kidney samples). Aggregates consisted of single elements (As, Ba, Cu, F, Fe, Ge, Hg, Ni, P, Pb, S, Si, Ti) or multiple association of elements, up to six. Silicon and Fe were the main element constituents (presence in 61% and 23% of the total Pags) followed by Al, Hg, Ni, Pb, and Ti (< 1%). Calcium, Cl, Co, Cr, Na, K, P, Sc, Sn, W, V, Zn, sometimes Mg, Rh, and Ta, were also detected. Overall, our findings suggest that the ubiquitous presence of metal species as particle aggregates in human tissues would be a condition of normality, although such presence per se is far from being used as a toxicity biomarker. Before being able to clarify the implications of particles in diseases or normal physiological processes, the biological meaning of particles background level we observed in liver and kidney must be elucidated.

Fabrication and characterization of chitosan conjugated eurycomanone nanoparticles: In vivo evaluation of the biodistribution and toxicity in fish

Chitosan nanoparticles (CNPs) have been proven considerable delivery agents due to their remarkable physicochemical properties. Present study reports the fabrication of CNPs by ionic gelation process and their characterization by different approaches. The constructed nanoparticles were successfully conjugated with eurycomanone with significant entrapment efficiency. Particle size of chitosan and chitosan conjugated eurycomanone nanoparticles were 126.2nm and 130nm respectively. Scanning electron microscopy showed that the particles were spherical in shape and well dispersed. Cross-linking between CNPs and eurycomanone (CENPs) were confirmed by Fourier-transform infrared (FTIR) spectroscopy. Fluorescent nanoparticles were prepared by using Rhodamine-6G dye, characterised by SEM and confirmed for conjugation by FTIR. Biodistribution of CENPs showed the presence of fluorescent nanoparticles in liver, kidney, testes and brain of C. magur. The toxicity of CENPs was evaluated by comparing the histological sections of catfish testes collected from treated and control group. No signs of toxicity were seen in testes after the delivery of CENPs. Molecular docking study revealed high spontaneous binding ability of chitosan with eurycomanone and aromatase enzyme. The study reports that CNPs can act as a stabilizing agent for eurycomanone formulation and could be a promising approach to increase the reproductive performance of the fishes.

Investigation of the toxicity of bismuth oxide nanoparticles in various cell lines

Nanoparticles have been drawn attention in various fields ranging from medicine to industry because of their physicochemical properties and functions, which lead to extensive human exposure to nanoparticles. Bismuth (Bi)-based compounds have been commonly used in the industrial, cosmetic and medical applications. Although the toxicity of Bi-based compounds was studied for years, there is a serious lack of information concerning their toxicity and effects in the nanoscale on human health and environment. Therefore, we aimed to investigate the toxic effects of Bi (III) oxide (Bi2O3) nanoparticles in liver (HepG2 hepatocarcinoma cell), kidney (NRK-52E kidney epithelial cell), intestine (Caco-2 colorectal adenocarcinoma cell), and lung (A549 lung carcinoma cell) cell cultures. Bi2O3 nanoparticles (∼149.1 nm) were easily taken by all cells and showed cyto- and genotoxic effects. It was observed that the main cell death pathways were apoptosis in HepG2 and NRK-52E cells and necrosis in A549 and Caco-2 cells exposed to Bi2O3 nanoparticles. Also, the glutathione (GSH), malondialdehyde (MDA), and 8-hydroxy deoxyguanine (8-OHdG) levels were significantly changed in HepG2, NRK-52E, and Caco-2 cells, except A549 cell. The present study is the first to evaluate the toxicity of Bi2O3 nanoparticles in mammalian cells. Bi2O3 nanoparticles should be thoroughly assessed for their potential hazardous effects to human health and the results should be supported with in vivo studies to fully understand the mechanism of their toxicity.

Synthesis, characterization and liver targeting evaluation of self-assembled hyaluronic acid nanoparticles functionalized with glycyrrhetinic acid

Recently, polymeric materials with multiple functions have drawn great attention as the carrier for drug delivery system design. In this study, a series of multifunctional drug delivery carriers, hyaluronic acid (HA)-glycyrrhetinic acid (GA) succinate (HSG) copolymers were synthesized via hydroxyl group modification of hyaluronic acid. It was shown that the HSG nanoparticles had sub-spherical shape, and the particle size was in the range of 152.6–260.7nm depending on GA graft ratio. HSG nanoparticles presented good short term and dilution stability. MTT assay demonstrated all the copolymers presented no significant cytotoxicity. In vivo imaging analysis suggested HSG nanoparticles had superior liver targeting efficiency and the liver targeting capacity was GA graft ratio dependent. The accumulation of DiR (a lipophilic, NIR fluorescent cyanine dye)-loaded HSG-6, HSG-12, and HSG-20 nanoparticles in liver was 1.8-, 2.1-, and 2.9-fold higher than that of free DiR. The binding site of GA on HA may influence liver targeting efficiency. These results indicated that HSG copolymers based nanoparticles are potential drug carrier for improved liver targeting.

SYNTHESIS AND TISSUE DISTRIBUTION OF COFE2O4 NANOPARTICLES COATED WITH DMSA IN RATS LIVER

Objective(s): According to the unique properties of magnetic nanoparticles, their usages in medicine and industry have increased in the last decade. Due to the vital role of liver in the body, the accumulation of CoFe2O4 and CoFe2O4@DMSA was studied. Materials and Methods:The nanoparticles were synthesized by co-precipitation method and were coated with DMSA. The techniques XRD, TEM, DLS, FTIR, AGFM and UV-Visible spectroscopy were used to characterize the nanoparticles. Nanoparticles were injected intraperitoneally in rat and blood samples were collected from the rats’ heart, at 15 and 30 day post injection. The liver of each rat was removed and kept frozen at -70 oC. Results:The size of the pure cobalt ferrite and DMSA coated cobalt ferrite nanoparticles were about 10 nm and 12 nm, respectively. The saturation magnetization of CoFe2O4 and CoFe2O4@DMSA nanoparticles were 44.8 and 33 emu/g, respectively. Statistical analysis of the results indicated that cobalt ferrite nanoparticles were accumulated in liver in all groups. Conclusion: The accumulation of nanoparticles in liver was significantly higher than those of the control group and the level of liver iron accumulation was significantly lower after 30 days of injection in comparison with 15 days post injection in all groups.

ABC transporters affect the elimination and toxicity of CdTe quantum dots in liver and kidney cells

This paper aimed to investigate the role of adenosine triphosphate-binding cassette (ABC) transporters on the efflux and the toxicity of nanoparticles in liver and kidney cells. In this study, we synthesized CdTe quantum dots (QDs) that were monodispersed and emitted green fluorescence (maximum peak at 530nm). Such QDs tended to accumulate in human hepatocellular carcinoma cells (HepG2), human kidney cells 2 (HK-2), and Madin-Darby canine kidney (MDCK) cells, and cause significant toxicity in all the three cell lines. Using specific inhibitors and inducers of P-glycoprotein (Pgp) and multidrug resistance associated proteins (Mrps), the cellular accumulation and subsequent toxicity of QDs in HepG2 and HK-2 cells were significantly affected, while only slight changes appeared in MDCK cells, corresponding well with the functional expressions of ABC transporters in cells. Moreover, treatment of QDs caused concentration- and time- dependent induction of ABC transporters in HepG2 and HK-2 cells, but such phenomenon was barely found in MDCK cells. Furthermore, the effects of CdTe QDs on ABC transporters were found to be greater than those of CdCl2 at equivalent concentrations of cadmium, indicating that the effects of QDs should be a combination of free Cd2+ and specific properties of QDs. Overall, these results indicated a strong dependence between the functional expressions of ABC transporters and the efflux of QDs, which could be an important reason for the modulation of QDs toxicity by ABC transporters.

Dose–Response Bioconversion and Toxicity Analysis of Magnetite Nanoparticles

Iron oxide nanoparticles are an innovative and promising tool in biomedical research. A prerequisite for clinical applications is a demonstration of safety. Magnetite nanoparticles, 10 nm in diameter, were obtained by thermal decomposition and coated with meso-2,3-dimercaptosuccinic acid (DMSA). The DMSA-coated particles were administered intravenously at dose levels of 2.5, 7.5, and 15 mg Fe/kg body weight. An extended, acute toxicity study was carried out over two weeks. We report clinical observations, body weight, food consumption, gross pathology, and biodistribution in the spleen and liver. The results suggest that these materials are safe for biomedical applications. Magnetic susceptibility measurements demonstrate an accumulation of nanoparticles in liver and spleen tissues for the highest dose, whereas they are not detectable for the lowest dose.

Systemic distribution and biological safety of mesoporous bioactive glass nanoparticles by 45Ca labeling, tracing, and histological evaluation

Event Abstract Back to Event Systemic distribution and biological safety of mesoporous bioactive glass nanoparticles by 45Ca labeling, tracing, and histological evaluation Baiyan Sui1, Gaoren Zhong1* and Jiao Sun1 1 Shanghai Jiaotong University School of Medicine, Shanghai Biomaterials Research & Testing Center, Ninth People’s Hospital, China Introduction: Mesoporous bioactive glass (MBG) nanoparticles had the advantage of high loading efficiency[1], but it is still unknown its state in vivo on early stage, which is directly bearing on pharmacodynamics and the organism’s biological risks. Therefore, it is necessary to explicit the distribution and potential risks to organism. In this study, the synthesis of MBG nanoparticle was introduced by radionuclide calcium (45Ca), the distribution of MBG nanoparticle in major tissues and organs was analyzed within 72 hours. Finally, whether MBG nanoparticle caused a histopathologic reaction was evaluated. Experimental Section: A hydrothermal method using 45Ca (NO3)2·4H2O, TEOS and TEP in combination with CTAB and PVP co-templates was applied to prepare 45Ca-MBG nanoparticles. MBG nanoparticles were characterized by transmission electron microscopy (TEM). The size and zeta potential in physiological saline were performed on a ZetaSizer. Then twenty ICR mice were intravenously injection by 45Ca-MBG nanoparticles. Then the blood, heart, lung, liver, spleen, and kidney were harvested, and the tissue distribution was expressed as the percentage injected dose per gram tissue (%ID/g). Finally ICR mice were injected via tail vein with nanoparticles (physiological saline set as control). After 72h, the major organs were collected, and the histopathological change was evaluated. Results and Discussion: The establishment of an effective labeling technique is considered to come first on monitoring the distribution of MBG nanoparticles in vivo. In this study, the size of obtained 45Ca-MBG nanoparticles with a mesostructure was in the range of 50-100 nm (Figure 1). The hydrodynamic size, increased by slightly agglomeration, was 177.7nm. The nanoparticles remained the low negative surface charge (-11.7mV) which may be suitable as a drug vehicle in clinical. Furthermore, the nanoparticles were mainly distributed in the blood and major organs (Figure 2). The radioactivity peaked at 12 hours and then declined gradually. The accumulation of MBG nanoparticles in liver was higher than that of other organs. This phenomenon could be interpreted that the size of MBG nanoparticles, which was smaller than the reticuloendothelial gap of liver, was in favor of intrahepatic transport[2]. Ultimately, there was no obvious pathological change in the major organs. Conclusion: This study has created an effective quantitative tracer for the 45Ca labeling of MBG nanoparticles. The results demonstrated that post injection in mice, 45Ca-MBG nanoparticles distributed in the heart, lungs, liver, spleen and kidneys through blood circulation, and did not cause histopathological changes. These findings preliminarily addressed the benefits and risks of MBG nanoparticles as nano drug delivery. Figure 1. TEM image for MBG nanoparticles Figure 2. Quantitative tissue distribution of 45Ca-MBG nanoparticle in major tissues

Kinetic analysis of superparamagnetic iron oxide nanoparticles in the liver of body-temperature-controlled mice using dynamic susceptibility contrast magnetic resonance imaging and an empirical mathematical model

The purpose of this study was to develop a method for analyzing the kinetic behavior of superparamagnetic iron oxide nanoparticles (SPIONs) in the murine liver under control of body temperature using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) and an empirical mathematical model (EMM).First, we investigated the influence of body temperature on the kinetic behavior of SPIONs in the liver by controlling body temperature using our temperature-control system. Second, we investigated the kinetic behavior of SPIONs in the liver when mice were injected with various doses of GdCl3, while keeping the body temperature at 36°C. Finally, we investigated it when mice were injected with various doses of zymosan, while keeping the body temperature at 36°C. We also investigated the effect of these substances on the number of Kupffer cells by immunohistochemical analysis using the specific surface antigen of Kupffer cells (CD68).To quantify the kinetic behavior of SPIONs in the liver, we calculated the upper limit of the relative enhancement (A), the rates of early contrast uptake (α) and washout or late contrast uptake (β), the parameter related to the slope of early uptake (q), the area under the curve (AUC), the maximum change of transverse relaxation rate (ΔR2) (ΔR2max), the time to ΔR2max (Tmax), and ΔR2 at the last time point (ΔR2last) from the time courses of ΔR2 using the EMM.The β and Tmax values significantly decreased and increased, respectively, with decreasing body temperature, suggesting that the phagocytic activity of Kupffer cells is significantly affected by body temperature. The AUC, ΔR2max, and ΔR2last values decreased significantly with increasing dose of GdCl3, which was consistent with the change in the number of CD68-positive cells. They increased with increasing dose of zymosan, which was also consistent with the change in the number of CD68-positive cells. These results suggest that AUC, ΔR2max, and ΔR2last reflect the number of Kupffer cells.In conclusion, we presented a method for analyzing the kinetic behavior of SPIONs in the liver using DSC-MRI and EMM, and investigated the influence of body temperature, GdCl3, and zymosan using body-temperature-controlled mice. The present study suggests that control of body temperature is essential for investigating the kinetic behavior of SPIONs in the liver and that our method will be applicable and useful for quantifying the responses of Kupffer cells to various drugs under control of body temperature.

GABA and 5-HT chitosan nanoparticles decrease striatal neuronal degeneration and motor deficits during liver injury

The metabolic alterations resulted from hepatic injury and cell loss lead to synaptic defects and neurodegeneration that undoubtedly contribute motor deficits. In the present study, GABA and 5-HT chitosan nanoparticles mediated liver cell proliferation influenced by growth factor and cytokines and neuronal survival in corpus striatum of partially hepatectomised rats was evaluated. Liver cell proliferation was initiated and progressed by the combined effect of increased expression of growth factor, insulin like growth factor-1 and decreased expressions of cytokines, tumor necrosis factor-α and Akt-1. This was confirmed by the extent of incorporation of thymidine analogue, BrdU, in the DNA of rapidly dividing cells. Inappropriate influx of compounds to corpus striatum resulting from incomplete metabolism elevated GABAB and 5-HT2A neurotransmissions compared to those treated with nanoparticles. This directly influenced cyclic AMP response element binding protein, glial cell derived neurotrophic factor and brain derived neurotrophic factor in the corpus striatum that facilitate neurogenesis, neuronal survival, development, differentiation and neuroprotection. Motor deficits due to liver injury followed striatal neuronal damage were scored by grid walk and rotarod studies, which confirmed the regain of motor activity by GABA and 5-HT chitosan nanoparticle treatment. The present study revealed the therapeutic significance of GABA and 5-HT chitosan nanoparticles in liver based diseases and related striatal neuronal damage that influenced by GABA and 5-HT.

The study of in vivo acute effect of two different delivery modalities of iron oxide core with titanium dioxide shell nanoparticles in rabbits liver tumor.

e22204 Background: To compare intravenous (IV) versus fluoroscopy-guided transarterial intra-catheter (IC) delivery of iron oxide core with titanium dioxide shell nanoparticles (NPs) in vivo in VX2 model of liver cancer in rabbits and detect the NPs distribution and effect of NPs presence on the target tumor and other rabbit’s organs. Methods: After obtaining the IACUC approval, liver tumors were obtained by implantation of tumor tissue obtained from a hind limb VX2 tumor of donor rabbits. NPs were delivered either IV or IC. After rabbit termination, 2 hours post NPs injection, tumor, liver, kidney, lung and spleen were harvested, split in half and a part of it was frozen while the remainder was formalin fixed and paraffin embedded. To assess the NPs distribution in 2D we stained 5um thick paraffin tissue sections using Dopamine-Biotin-DHS histochemical (HC) staining followed by Nanozoomer microscopy analysis. H and E staining, TUNEL assay and Ki67 immunohistochemistry were also done. X-ray Fluorescence Microscopy (XFM) was used to quantify the NPs. Frozen tissue was used for bulk NPs concentration analysis using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Results: This study included ten rabbits; 3 rabbits had IV NPs injections, 3 had IC NPs injection, 2 control and 2 donors. ICP-MS analysis showed statistically significant higher NPs concentration in tumors of IC arm vs. IV arm (p= 0.0356), while there was higher concentration of NPs in liver (p=0.00077) and spleen (p = 0.01356) of IV vs. IC arms but no difference in kidneys or lungs. These findings were consistent with results from HC and XFM analyses. HC 2D analysis of NPs distribution showed that the RES have taken up the NPs non-specifically. There were no statistically significant differences between the treatment groups regarding the Ki67 proliferation or the TUNEL apoptosis indices or when control rabbits were compared to NPs treated rabbits. Conclusions: Both IV and IC NPs injection are feasible modalities for delivering NPs to tumors with acceptable acute systemic effects and comparable tumor effect. IV delivery increased sequestration of the NPs by RES and their accumulation in spleen and liver.

Radioisotope post-labeling upconversion nanophosphors for in vivo quantitative tracking

Lanthanide based upconversion nanophosphors (UCNPs) attracted increasing attention for potential applications in bioimaging, while its in vivo behaviors are not clear until now due to no available quantification imaging tools. Herein, we developed a unique rare-earth cation-exchange-based postlabelling method to introduce 153Sm into the lattice of UCNPs, providing this 153Sm-postlabeling UCNP having bifunction of radioactive property and upconversion luminescence under excitation at 980 nm laser. This 153Sm-postlabelling method shows rapid treatment time of <1 min, high labeling yield of >99%, and without usage of organic solvents. More importantly, this 153Sm-postlabelling method is also suitable for most of rare earth nanoparticles to track their in vivo behaviors. The dynamic quantification studies of the in vivo fate of the rare-earth nanoparticles were further investigated by radioactive detection method such as single-photon emission computed tomography (SPECT) and gamma counter. The imaging results revealed that UCNPs were mainly captured by the mononuclear phagocyte system (liver and spleen). The amount of nanoparticles in liver arrived at its peak quicker and was about 15 fold of that in spleen. And the nanoparticles will be slowly excreted with the bile. Therefore, the concept of postlabeling 153Sm onto lanthanide-based UCNPs may serve as a facile strategy of fabricating multifunctional nanoprobes for upconversion luminescence (UCL) and SPECT dual-modality imaging.

Visualisation of distribution of gold nanoparticles in liver tissues ex vivo and in vitro using the method of optical coherence tomography

The possibility of visualising the distribution of gold nanoparticles in liver by means of the method of optical coherence tomography is studied experimentally in model samples of beef liver in vitro and rat liver ex vivo. In the experiments we used the gold nanoparticles in the form of nanocages with resonance absorption in the near-IR spectral region. In the model studies the suspension of nanoparticles was applied to the surface of the sample, which then was treated with ultrasound. In the ex vivo studies the suspension of nanoparticles was injected to the laboratory rats intravenously. The image contrast and the optical depth of detection of blood vessels and liver structure components are calculated, as well as the depth of liver optical probing before and after the injection of nanoparticles. It was shown that the administration ofthe nanoparticle increases significantly the imaging contrast of liver blood vessels owing to the localisation of the nanoparticles therein.

Rapid analysis of gold nanoparticles in liver and river water samples

This paper describes a simple approach to determine gold nanoparticles in liver and river water samples. The method of purification of nanoparticles from the matrix is based on the stabilization of gold nanoparticles with a cationic surfactant followed by a microliquid-liquid extraction in ionic liquid. Finally, the extracted nanoparticles can be analysed by UV/Vis detection or Raman spectroscopy. The precision of the proposed method for the analysis of liver tissue and river water samples was 9.7% and 18% respectively for UV/Vis analysis. The sensitivity was 1.17 × 10(-12) M for the analysis of 3 mL of liver homogenate or river water sample.