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1.
In the copper metallurgy workplace air is polluted with condensation aerosols, which a significant fraction of is presented by copper oxide particles <100 nm. In the scientific literature, there is a lack of their in vivo toxicity characterization and virtually no attempts of enhancing organism’s resistance to their impact. A stable suspension of copper oxide particles with mean (±SD) diameter 20 ± 10 nm was prepared by laser ablation of pure copper in water. It was being injected intraperitoneally to rats at a dose of 10 mg/kg (0.5 mg per mL of deionized water) three times a week up to 19 injections. In parallel, another group of rats was so injected with the same suspension against the background of oral administration of a “bio-protective complex” (BPC) comprising pectin, a multivitamin-multimineral preparation, some amino acids and fish oil rich in ω-3 PUFA. After the termination of injections, many functional and biochemical indices for the organism’s status, as well as pathological changes of liver, spleen, kidneys, and brain microscopic structure were evaluated for signs of toxicity. In the same organs we have measured accumulation of copper while their cells were used for performing the Random Amplification of Polymorphic DNA (RAPD) test for DNA fragmentation. The same features were assessed in control rats infected intraperitoneally with water with or without administration of the BPC. The copper oxide nanoparticles proved adversely bio-active in all respects considered in this study, their active in vivo solubilization in biological fluids playing presumably an important role in both toxicokinetics and toxicodynamics. The BPC proposed and tested by us attenuated systemic and target organs toxicity, as well as genotoxicity of this substance. Judging by experimental data obtained in this investigation, occupational exposures to nano-scale copper oxide particles can present a significant health risk while the further search for its management with the help of innocuous bioprotectors seems to be justified.  相似文献   

2.
Iron oxide nanoparticles (NPs) are commonly utilized for biomedical, industrial, and commercial applications due to their unique properties and potential biocompatibility. However, little is known about how exposure to iron oxide NPs may affect susceptible populations such as pregnant women and developing fetuses. To examine the influence of NP surface-charge and dose on the developmental toxicity of iron oxide NPs, Crl:CD1(ICR) (CD-1) mice were exposed to a single, low (10 mg/kg) or high (100 mg/kg) dose of positively-charged polyethyleneimine-Fe2O3-NPs (PEI-NPs), or negatively-charged poly(acrylic acid)-Fe2O3-NPs (PAA-NPs) during critical windows of organogenesis (gestation day (GD) 8, 9, or 10). A low dose of NPs, regardless of charge, did not induce toxicity. However, a high exposure led to charge-dependent fetal loss as well as morphological alterations of the uteri (both charges) and testes (positive only) of surviving offspring. Positively-charged PEI-NPs given later in organogenesis resulted in a combination of short-term fetal loss (42%) and long-term alterations in reproduction, including increased fetal loss for second generation matings (mice exposed in utero). Alternatively, negatively-charged PAA-NPs induced fetal loss (22%) earlier in organogenesis to a lesser degree than PEI-NPs with only mild alterations in offspring uterine histology observed in the long-term.  相似文献   

3.
The objective of the present study was to define whether inhaled tetrandrine (TET) could be a promising way to achieve the local effect on its therapeutic efficacy based on biodistribution features using the LPS-treated acute lung injury (ALI) model. The tissue distribution profiles of inhaled TET in normal and ALI mouse models showed that pulmonary inflammation led to an altered distribution in a tissue-specific way. More TET accumulated in almost all tissues including in the blood. Among them, the increased exposure in the lungs was significantly higher than in the other tissues. However, there was a negative increase in the brain. In vitro turnover rates of TET in mouse liver microsomes (MLM) from normal and LPS-treated mice showed significant differences. In the presence of NADPH, TET demonstrated relatively low hepatic clearance (89 mL/h/kg) in that of normal MLM (140 mL/h/kg). Intracellular uptakes of TET in A549, HepG2, RAW264.7, and C8-D1A cells were significantly inhibited by monensin, indicating that the intracellular accumulation of TET is driven by lysosomal trapping. However, in the presence of LPS, only the lysosomal pH partitioning of TET in A549 cell lines increased (~30%). Bidirectional transport of TET across LLC-PK1 cell expressing MDR1 showed that MDR1 is responsible for the low brain exposure via effluxion (ER = 32.46). From the observed overall agreement between the in vitro and in vivo results, we concluded that the downregulation of the CYP3A together with strengthened pulmometry lysosomal trapping magnified the retention of inhaled TET in the lung. These results therefore open the possibility of prolonging the duration of the local anti-inflammation effect against respiratory disorders.  相似文献   

4.
Zinc oxide (ZnO) nanoparticles are widely used in various products, and the safety evaluation of this manufactured material is important. The present study investigated the inflammatory and fibrotic effects of pulmonary exposure to ZnO nanoparticles in a mouse model of pulmonary fibrosis. Pulmonary fibrosis was induced by constant subcutaneous infusion of bleomycin (BLM). Female C57BL/6Jcl mice were divided into BLM-treated and non-treated groups. In each treatment group, 0, 10, 20 or 30 µg of ZnO nanoparticles were delivered into the lungs through pharyngeal aspiration. Bronchoalveolar lavage fluid (BALF) and the lungs were sampled at Day 10 or 14 after administration. Pulmonary exposure by a single bolus of ZnO nanoparticles resulted in severe, but transient inflammatory infiltration and thickening of the alveolar septa in the lungs, along with the increase of total and differential cell counts in BLAF. The BALF level of interleukin (IL)-1β and transforming growth factor (TGF)-β was increased at Day 10 and 14, respectively. At Day 10, the synergistic effect of BLM and ZnO exposure was detected on IL-1β and monocyte chemotactic protein (MCP)-1 in BALF. The present study demonstrated the synergistic effect of pulmonary exposure to ZnO nanoparticles and subcutaneous infusion of BLM on the secretion of pro-fibrotic cytokines in the lungs.  相似文献   

5.
The prostate‐specific membrane antigen (PSMA) is an established target for the delivery of cancer therapeutic and imaging agents due to its high expression on the surface of prostate cancer cells and within the neovasculature of other solid tumors. Here, we describe the synthesis and screening of antibody‐conjugated silica‐coated iron oxide nanoparticles for PSMA‐specific cell targeting. The humanized anti‐PSMA antibody, HuJ591, was conjugated to a series of nanoparticles with varying densities of polyethylene glycol and primary amine groups. Customized assays utilizing iron spectral absorbance and enzyme‐linked immunoassay (ELISA) were developed to screen microgram quantities of nanoparticle formulations for immunoreactivity and cell targeting ability. Antibody and PSMA‐specific targeting of the optimized nanoparticle was evaluated using an isogenic PSMA‐positive and PSMA‐negative cell line pair. Specific nanoparticle targeting was confirmed by iron quantification with inductively coupled plasma mass spectrometry (ICP‐MS). These methods and nanoparticles support the promise of targeted theranostic agents for future treatment of prostate and other cancers.  相似文献   

6.
7.
Due to their potent antibacterial properties, silver nanoparticles (AgNPs) are widely used in industry and medicine. However, they can cross the brain–blood barrier, posing a risk to the brain and its functions. In our previous study, we demonstrated that oral administration of bovine serum albumin (BSA)-coated AgNPs caused an impairment in spatial memory in a dose-independent manner. In this study, we evaluated the effects of AgNPs coating material on cognition, spatial memory functioning, and neurotransmitter levels in rat hippocampus. AgNPs coated with BSA (AgNPs(BSA)), polyethylene glycol (AgNPs(PEG)), or citrate (AgNPs(Cit)) or silver ions (Ag+) were orally administered at a dose of 0.5 mg/kg b.w. to male Wistar rats for a period of 28 days, while the control (Ctrl) rats received 0.2 mL of water. The acquisition and maintenance of spatial memory related to place avoidance were assessed using the active allothetic place avoidance task, in which rats from AgNPs(BSA), AgNPs(PEG), and Ag+ groups performed worse than the Ctrl rats. In the retrieval test assessing long-term memory, only rats from AgNPs(Cit) and Ctrl groups showed memory maintenance. The analysis of neurotransmitter levels indicated that the ratio between serotonin and dopamine concentration was disturbed in the AgNPs(BSA) rats. Furthermore, treatment with AgNPs or Ag+ resulted in the induction of peripheral inflammation, which was reflected by the alterations in the levels of serum inflammatory mediators. In conclusion, depending on the coating material used for their stabilization, AgNPs induced changes in memory functioning and concentration of neurotransmitters.  相似文献   

8.
The environmental pollutant benzo[a]pyrene (BaP) is a human carcinogen that reacts with DNA after metabolic activation catalysed by cytochromes P450 (CYP) 1A1 and 1B1 together with microsomal epoxide hydrolase. The azo dye Sudan I is a potent inducer of CYP1A1/2. Here, Wistar rats were either treated with single doses of BaP (150 mg/kg bw) or Sudan I (50 mg/kg bw) alone or with both compounds in combination to explore BaP-derived DNA adduct formation in vivo. Using 32P-postlabelling, DNA adducts generated by BaP-7,8-dihydrodiol-9,10-epoxide were found in livers of rats treated with BaP alone or co-exposed to Sudan I. During co-exposure to Sudan I prior to BaP treatment, BaP-DNA adduct levels increased 2.1-fold in comparison to BaP treatment alone. Similarly, hepatic microsomes isolated from rats exposed to Sudan I prior to BaP treatment were also the most effective in generating DNA adducts in vitro with the activated metabolites BaP-7,8-dihydrodiol or BaP-9-ol as intermediates. DNA adduct formation correlated with changes in the expression and/or enzyme activities of CYP1A1, 1A2 and 1B1 in hepatic microsomes. Thus, BaP genotoxicity in rats in vivo appears to be related to the enhanced expression and/or activity of hepatic CYP1A1/2 and 1B1 caused by exposure of rats to the studied compounds. Our results indicate that the industrially employed azo dye Sudan I potentiates the genotoxicity of the human carcinogen BaP, and exposure to both substances at the same time seems to be hazardous to humans.  相似文献   

9.
Simvastatin (SIM) is a lipid-lowering drug that also promotes bone formation, but its high liver specificity may cause muscle damage, and the low solubility of lipophilic drugs limits the systemic administration of SIM, especially in osteoporosis (OP) studies. In this study, we utilized the bone-targeting moiety of dendritic oligopeptides consisting of three aspartic acid moieties (dAsp3) and amphiphilic polymers (poly(ethylene glycol)-block-poly(lactic-co-glycolic acid); PEG-PLGA) to create dAsp3-PEG-PLGA (APP) nanoparticles (NPs), which can carry SIM to treat OP. An in vivo imaging system showed that gold nanocluster (GNC)-PLGA/APP NPs had a significantly higher accumulation rate in representative bone tissues. In vivo experiments comparing low-dose SIM treatment (0.25 mg/kg per time, 2 times per week) showed that bone-targeting SIM/APP NPs could increase the bone formation effect compared with non-bone-targeting SIM/PP NPs in a local bone loss of hindlimb suspension (disuse) model, but did not demonstrate good bone formation in a postmenopausal (ovariectomized) model of systemic bone loss. The APP NPs could effectively target high mineral levels in bone tissue and were expected to reduce side effects in other organs affected by SIM. However, in vivo OP model testing showed that the same lower dose could not be used to treat different types of OP.  相似文献   

10.
In this study, a commercial polyamide nanofiltration membrane was modified by a combination of poly(ethylene glycol) diacrylate (PEGDA) in situ polymerization and silica (SiO2) nanoparticles. The PEGDA layer was polymerized on the surface of the membranes alone or mixed with SiO2 nanoparticle. The surface modification influence on the water flux, salt rejection, and antifouling behavior was investigated. The effects of the nanoparticles and PEGDAylation on the membrane properties were characterized by Fourier transform infrared spectroscopy, contact angle measurement, and scanning electron microscopy analyses. The membranes that were in contact with 30 wt % PEGDA and then treated with ultraviolet light for 5 min had a better water flux than the unmodified membrane. The fouling resistance of the membranes to a foulant solution containing bovine serum albumin, humic acid, and sodium sulfate were studied, and the results show that the membrane with 30 wt % PEGDA had better antifouling properties. After the weight percentage of PEGDA for the prepolymerization solution was optimized (30 wt % was the best), the SiO2 nanoparticle concentration in the prepolymerization matrix was optimized. The presence of SiO2 nanoparticles in the PEGDA layer increased the membrane flux. The maximum water flux and good antifouling properties were obtained for 0.5 wt % SiO2 nanoparticles in a 30 wt % PEGDA layer. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43793.  相似文献   

11.
A one‐step electrode surface modification is proposed in which a disposable, screen‐printed carbon electrode is functionalized with carbonized, electrospun polyacrylonitrile (PAN)‐loaded graphene (G) nanoparticles to form a composite, CPAN5G‐4x. The electrochemical behavior of the CPAN5G‐4x electrode was examined by cyclic voltammetry and electrochemical impedance spectroscopy. Scanning electron microscopy and X‐ray diffraction were used to characterize the surface morphology and physical properties of the carbonized composite nanofibers before and after modification. The modified electrode was found to be effective for the detection of dopamine (DA) using square‐wave voltammetry (SWV) in the presence of interfering substances such as ascorbic acid and uric acid. With the addition of sodium dodecyl sulfate (SDS) to an optimized solution of phosphate‐buffered saline (PBS) at a pH of 2, the fabricated electrode exhibited enhanced electrocatalytic activity toward the oxidation of DA relative to PBS without SDS at a pH of 7.4. The SWV current displayed a linear response to DA concentrations ranging from 0.5 to 100 μM, with a limit of detection of 70 nM (S/N = 3) and a sensitivity of 1.4258 μA μM?1 cm?2. Finally, the CPAN5G‐4x electrode was used to determine DA levels in human serum. The modified electrode can potentially be harnessed for further electrochemical biosensor applications. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40858.  相似文献   

12.
The FMS-like tyrosine kinase 3 (FLT3) gene is mutated in one-third of patients with de novo acute myeloid leukemia (AML). Mutated FLT3 variants are constitutively active kinases signaling via AKT kinase, MAP kinases, and STAT5. FLT3 inhibitors have been approved for the treatment of FLT3-mutated AML. However, treatment response to FLT3 inhibitors may be short-lived, and resistance may emerge. Compounds targeting STAT5 may enhance and prolong effects of FLT3 inhibitors in this subset of patients with FLT3-mutated AML. Here STAT5-inhibitor AC-4-130, FLT3 inhibitor midostaurin (PKC412), BMI-1 inhibitor PTC596, MEK-inhibitor trametinib, MCL1-inhibitor S63845, and BCL-2 inhibitor venetoclax were assessed as single agents and in combination for their ability to induce apoptosis and cell death in leukemic cells grown in the absence or presence of bone marrow stroma. Synergistic effects on cell viability were detected in both FLT3-mutated and FLT3-wild-type AML cells treated with AC-4-130 in combination with the MCL1 inhibitor S63845. AML patient samples with a strong response to AC-4-130 and S63845 combination treatment were characterized by mutated FLT3 or mutated TET2 genes. Susceptibility of AML cells to AC-4-130, PTC596, trametinib, PKC412, and venetoclax was altered in the presence of HS-5 stroma. Only the MCL1 inhibitor S63845 induced cell death with equal efficacy in the absence or presence of bone marrow stroma. The combination of the STAT5-inhibitor AC-4-130 and the MCL1 inhibitor S63845 may be an effective treatment targeting FLT3-mutated or TET2-mutated AML.  相似文献   

13.
ATRP in the design of functional materials for biomedical applications   总被引:1,自引:0,他引:1  
Atom Transfer Radical Polymerization (ATRP) is an effective technique for the design and preparation of multifunctional, nanostructured materials for a variety of applications in biology and medicine. ATRP enables precise control over macromolecular structure, order, and functionality, which are important considerations for emerging biomedical designs. This article reviews recent advances in the preparation of polymer-based nanomaterials using ATRP, including polymer bioconjugates, block copolymer-based drug delivery systems, cross-linked microgels/nanogels, diagnostic and imaging platforms, tissue engineering hydrogels, and degradable polymers. It is envisioned that precise engineering at the molecular level will translate to tailored macroscopic physical properties, thus enabling control of the key elements for realized biomedical applications.  相似文献   

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