Glutathione protected bimetallic gold-platinum nanoclusters with near-infrared emission for ratiometric determination of silver ions.

A controlled method to prepare glutathione-protected bimetallic gold-platinum nanoclusters (Au-PtNCs) has been established. The Au-PtNCs show either strong red (625 nm) or near-infrared (NIR, 805 nm) emission. Further characterizations indicated that the average particle size grows from 1.42 to 1.78 nm, the larger particles being responsible for the redshift of emission. The NIR emitted Au-PtNCs are applied as a novel ratiometric probe of Ag(I), which induces a new emission peak at ~635 nm and quenches the initial emission gradually. The determination shows very high selectivity toward Ag(I) among other metal ions. A limit of determination (10 nM) and the linear range (0.10 to 15 µM) are achieved, which is much lower than the EPA mandate of 0.46 µM for Ag(I) in drinking water. The response mechanism is attributed to the fact that the added Ag(I) has been reduced by the core of Au-PtNCs and deposited on the surface, which induces new fluorescence emission around 635 nm. In addition, the ratiometric method is feasible for Ag(I) determination in serum serum with good recovery (between 98.3% and 102.0%, n = 3), showing very high application potential. The present study provides a controlled method to prepare Au-PtNCs with strong red and NIR emission and supplies a novel NIR ratiometric probe of Ag(I). Schematic presentation of the controlled preparation of glutathione-protected bimetallic gold-platinum nanoclusters (Au-PtNCs) with either red or near-infrared (NIR) emission, and application in ratiometric detection of Ag(I) with high selectivity and sensitivity.

Quantitative biokinetics over a 28 day period of freshly generated, pristine, 20 nm silver nanoparticle aerosols in healthy adult rats after a single 1½-hour inhalation exposure.

BACKGROUND: There is a steadily increasing quantity of silver nanoparticles (AgNP) produced for numerous industrial, medicinal and private purposes, leading to an increased risk of inhalation exposure for both professionals and consumers. Particle inhalation can result in inflammatory and allergic responses, and there are concerns about other negative health effects from either acute or chronic low-dose exposure. RESULTS: To study the fate of inhaled AgNP, healthy adult rats were exposed to 1½-hour intra-tracheal inhalations of pristine 105Ag-radiolabeled, 20 nm AgNP aerosols (with mean doses across all rats of each exposure group of deposited NP-mass and NP-number being 13.5 ± 3.6 µg, 7.9 ± 3.2•1011, respectively). At five time-points (0.75 h, 4 h, 24 h, 7d, 28d) post-exposure (p.e.), a complete balance of the [105Ag]AgNP fate and its degradation products were quantified in organs, tissues, carcass, lavage and body fluids, including excretions. Rapid dissolution of [105Ag]Ag-ions from the [105Ag]AgNP surface was apparent together with both fast particulate airway clearance and long-term particulate clearance from the alveolar region to the larynx. The results are compatible with evidence from the literature that the released [105Ag]Ag-ions precipitate rapidly to low-solubility [105Ag]Ag-salts in the ion-rich epithelial lining lung fluid (ELF) and blood. Based on the existing literature, the degradation products rapidly translocate across the air-blood-barrier (ABB) into the blood and are eliminated via the liver and gall-bladder into the small intestine for fecal excretion. The pathway of [105Ag]Ag-salt precipitates was compatible with auxiliary biokinetics studies at 24 h and 7 days after either intravenous injection or intratracheal or oral instillation of [110mAg]AgNO3 solutions in sentinel groups of rats. However, dissolution of [105Ag]Ag-ions appeared not to be complete after a few hours or days but continued over two weeks p.e. This was due to the additional formation of salt layers on the [105Ag]AgNP surface that mediate and prolonge the dissolution process. The concurrent clearance of persistent cores of [105Ag]AgNP and [105Ag]Ag-salt precipitates results in the elimination of a fraction > 0.8 (per ILD) after one week, each particulate Ag-species accounting for about half of this. After 28 days p.e. the cleared fraction rises marginally to 0.94 while 2/3 of the remaining [105Ag]AgNP are retained in the lungs and 1/3 in secondary organs and tissues with an unknown partition of the Ag species involved. However, making use of our previous biokinetics studies of poorly soluble [195Au]AuNP of the same size and under identical experimental and exposure conditions (Kreyling et al., ACS Nano 2018), the kinetics of the ABB-translocation of [105Ag]Ag-salt precipitates was estimated to reach a fractional maximum of 0.12 at day 3 p.e. and became undetectable 16 days p.e. Hence, persistent cores of [105Ag]AgNP were cleared throughout the study period. Urinary [105Ag]Ag excretion is minimal, finally accumulating to 0.016. CONCLUSION: The biokinetics of inhaled [105Ag]AgNP is relatively complex since the dissolving [105Ag]Ag-ions (a) form salt layers on the [105Ag]AgNP surface which retard dissolution and (b) the [105Ag]Ag-ions released from the [105Ag]AgNP surface form poorly-soluble precipitates of [105Ag]Ag-salts in ELF. Therefore, hardly any [105Ag]Ag-ion clearance occurs from the lungs but instead [105Ag]AgNP and nano-sized precipitated [105Ag]Ag-salt are cleared via the larynx into GIT and, in addition, via blood, liver, gall bladder into GIT with one common excretional pathway via feces out of the body.

Pulmonary toxicity of silver vapours, nanoparticles and fine dusts: A review.

Silver is used in a wide range of products, and during their production and use, humans may be exposed through inhalation. Therefore, it is critical to know the concentration levels at which adverse effects may occur. In rodents, inhalation of silver nanoparticles has resulted in increased silver in the lungs, lymph nodes, liver, kidney, spleen, ovaries, and testes. Reported excretion pathways of pulmonary silver are urinary and faecal excretion. Acute effects in humans of the inhalation of silver include lung failure that involved increased heart rate and decreased arterial blood oxygen pressure. Argyria-a blue-grey discoloration of skin due to deposited silver-was observed after pulmonary exposure in 3 individuals; however, the presence of silver in the discolorations was not tested. Argyria after inhalation seems to be less likely than after oral or dermal exposure. Repeated inhalation findings in rodents have shown effects on lung function, pulmonary inflammation, bile duct hyperplasia, and genotoxicity. In our evaluation, the range of NOAEC values was 0.11-0.75 mg/m3. Silver in the ionic form is likely more toxic than in the nanoparticle form but that difference could reflect their different biokinetics. However, silver nanoparticles and ions have a similar pattern of toxicity, probably reflecting that the effect of silver nanoparticles is primarily mediated by released ions. Concerning genotoxicity studies, we evaluated silver to be positive based on studies in mammalian cells in vitro and in vivo when considering various exposure routes. Carcinogenicity data are absent; therefore, no conclusion can be provided on this endpoint.

Early Postnatal Exposure to a Low Dose of Nanoparticulate Silver Induces Alterations in Glutamate Transporters in Brain of Immature Rats.

Due to strong antimicrobial properties, silver nanoparticles (AgNPs) are used in a wide range of medical and consumer products, including those dedicated for infants and children. While AgNPs are known to exert neurotoxic effects, current knowledge concerning their impact on the developing brain is scarce. During investigations of mechanisms of neurotoxicity in immature rats, we studied the influence of AgNPs on glutamate transporter systems which are involved in regulation of extracellular concentration of glutamate, an excitotoxic amino acid, and compared it with positive control-Ag citrate. We identified significant deposition of AgNPs in brain tissue of exposed rats over the post-exposure time. Ultrastructural alterations in endoplasmic reticulum (ER) and Golgi complexes were observed in neurons of AgNP-exposed rats, which are characteristics of ER stress. These changes presumably underlie substantial long-lasting downregulation of neuronal glutamate transporter EAAC1, which was noted in AgNP-exposed rats. Conversely, the expression of astroglial glutamate transporters GLT-1 and GLAST was not affected by exposure to AgNPs, but the activity of the transporters was diminished. These results indicate that even low doses of AgNPs administered during an early stage of life create a substantial risk for health of immature organisms. Hence, the safety of AgNP-containing products for infants and children should be carefully considered.

Silver absorption and toxicity evaluation of silver wound dressings in 40 patients with chronic wounds.

BACKGROUND: Silver-containing dressings are considered to be safe even though there have been some reports of complications, including argyria and various organ system dysfunctions. Despite the widespread use of silver dressings, little research has been done regarding the absorption and toxicity of silver. OBJECTIVE: We aimed to study the systemic absorption of silver in patients with chronic inflammatory wounds and to determine associated factors of systemic silver absorption and evaluated its association with silver toxicity. PATIENTS AND METHOD: Prospective, longitudinal, observational, multicentre, open-label pilot study. Patients from the Dermatology Departments of Lorraine (France) with the following inclusion criteria: (i) a chronic wound of more than 6 weeks and (ii) an ulcer needing silver-containing dressing were included. Before and after 28 days of treatment, clinical characteristics of the wound were recorded; hemogram, hepatic and renal functions, albumin sera and serum silver level were measured. RESULTS: Half of the cases displayed raised levels of silver after 1 month of treatment. Predictive factors for systemic silver absorption were wound area, anaemia and malnutrition with anaemia and malnutrition confirmed on multivariate analysis. Wound vascularization may also play a role, as a higher absorption was observed in cases of wound granulation without arterial components. No toxicity was detected. This work has also emphasized the slow elimination of silver from the body. CONCLUSION: Both long-term application and iterative treatments with silver dressings should be discouraged, especially in the elderly, who often suffer from malnutrition and anaemia to avoid potential cumulative toxicity.

Nanoparticle Enhanced Laser-Induced Breakdown Spectroscopy for Microdrop Analysis at subppm Level.

In this paper, nanoparticle enhanced laser-induced breakdown spectroscopy (NELIBS) was applied to the elemental chemical analysis of microdrops of solutions with analyte concentration at subppm level. The effect on laser ablation of the strong local enhancement of the electromagnetic field allows enhancing the optical emission signal up to more than 1 order of magnitude, enabling LIBS to quantify ppb concentration and notably decreasing the limit of detection (LOD) of the technique. At optimized conditions, it was demonstrated that NELIBS can reach an absolute LOD of few picograms for Pb and 0.2 pg for Ag. The effect of field enhancement in NELIBS was tested on biological solutions such as protein solutions and human serum, in order to improve the sensitivity of LIBS with samples where the formation and excitation of the plasma are not as efficient as with metals. Even in these difficult cases, a significant improvement with respect to conventional LIBS was observed.

Hydrodynamic chromatography coupled to single-particle ICP-MS for the simultaneous characterization of AgNPs and determination of dissolved Ag in plasma and blood of burn patients.

Silver nanoparticles (AgNPs) are increasingly used in medical devices as innovative antibacterial agents, but no data are currently available on their chemical transformations and fate in vivo in the human body, particularly on their potential to reach the circulatory system. To study the processes involving AgNPs in human plasma and blood, we developed an analytical method based on hydrodynamic chromatography (HDC) coupled to inductively coupled plasma mass spectrometry (ICP-MS) in single-particle detection mode. An innovative algorithm was implemented to deconvolute the signals of dissolved Ag and AgNPs and to extrapolate a multiparametric characterization of the particles in the same chromatogram. From a single injection, the method provides the concentration of dissolved Ag and the distribution of AgNPs in terms of hydrodynamic diameter, mass-derived diameter, number and mass concentration. This analytical approach is robust and suitable to study quantitatively the dynamics and kinetics of AgNPs in complex biological fluids, including processes such as agglomeration, dissolution and formation of protein coronas. The method was applied to study the transformations of AgNP standards and an AgNP-coated dressing in human plasma, supported by micro X-ray fluorescence (µXRF) and micro X-ray absorption near-edge spectroscopy (µXANES) speciation analysis and imaging, and to investigate, for the first time, the possible presence of AgNPs in the blood of three burn patients treated with the same dressing. Together with our previous studies, the results strongly support the hypothesis that the systemic mobilization of the metal after topical administration of AgNPs is driven by their dissolution in situ. Graphical Abstract Simplified scheme of the combined analytical approach adopted for studying the chemical dynamics of AgNPs in human plasma/blood.

Tissue distribution and acute toxicity of silver after single intravenous administration in mice: nano-specific and size-dependent effects.

BACKGROUND: Silver nanoparticles (AgNPs) are an important class of nanomaterials used as antimicrobial agents for a wide range of medical and industrial applications. However toxicity of AgNPs and impact of their physicochemical characteristics in in vivo models still need to be comprehensively characterized. The aim of this study was to investigate the effect of size and coating on tissue distribution and toxicity of AgNPs after intravenous administration in mice, and compare the results with those obtained after silver acetate administration. METHODS: Male CD-1(ICR) mice were intravenously injected with AgNPs of different sizes (10 nm, 40 nm, 100 nm), citrate-or polyvinylpyrrolidone-coated, at a single dose of 10 mg/kg bw. An equivalent dose of silver ions was administered as silver acetate. Mice were euthanized 24 h after the treatment, and silver quantification by ICP-MS and histopathology were performed on spleen, liver, lungs, kidneys, brain, and blood. RESULTS: For all particle sizes, regardless of their coating, the highest silver concentrations were found in the spleen and liver, followed by lung, kidney, and brain. Silver concentrations were significantly higher in the spleen, lung, kidney, brain, and blood of mice treated with 10 nm AgNPs than those treated with larger particles. Relevant toxic effects (midzonal hepatocellular necrosis, gall bladder hemorrhage) were found in mice treated with 10 nm AgNPs, while in mice treated with 40 nm and 100 nm AgNPs lesions were milder or negligible, respectively. In mice treated with silver acetate, silver concentrations were significantly lower in the spleen and lung, and higher in the kidney than in mice treated with 10 nm AgNPs, and a different target organ of toxicity was identified (kidney). CONCLUSIONS: Administration of the smallest (10 nm) nanoparticles resulted in enhanced silver tissue distribution and overt hepatobiliary toxicity compared to larger ones (40 and 100 nm), while coating had no relevant impact. Distinct patterns of tissue distribution and toxicity were observed after silver acetate administration. It is concluded that if AgNPs become systemically available, they behave differently from ionic silver, exerting distinct and size-dependent effects, strictly related to the nanoparticulate form.

First Clinical Experience With Thermal-Sprayed Silver Oxide-Containing Hydroxyapatite Coating Implant.

BACKGROUND: Prosthetic joint infection is a serious complication of implant therapy. To prevent prosthetic joint infection, we previously reported the features of silver oxide-containing hydroxyapatite (Ag-HA), which was prepared by mixing silver (a metal with antimicrobial activity) with HA. In this study, we evaluated the potential issues of total hip arthroplasty (THA) with an Ag-HA-coated implant. METHODS: We prepared an implant for THA that was coated with Ag-HA. In this study, the implant contained silver at a maximum quantity of 2.9 mg/implant. In this prospective interventional study, we performed THA with this implant in 20 patients and investigated the effects of silver. RESULTS: Blood silver levels peaked at 2 weeks after THA and gradually decreased thereafter. The highest blood silver level recorded during the postoperative follow-up was 6.0 ng/mL, which was within the normal range. The Harris Hip Scores increased in all cases, and activities of daily living improved markedly after THA with Ag-HA-coated implants. Implant failure was absent on radiography. No adverse reaction to silver was noted, and argyria was not observed in any case. No patients have developed infection after surgery. CONCLUSION: This is the first clinical study of Ag-HA-coated implants in THA. Our Ag-HA-coated implants markedly improved patients' activities of daily living without causing any adverse reactions attributable to silver in the human body. Ag-HA is expected to reduce postoperative infections and prevent decreased quality of life in patients undergoing prosthetic arthroplasty, thus leading to more favorable outcomes.

Neurotoxicity of Silver Nanoparticles in Rat Brain After Intragastric Exposure.

It is known that the biological half-life of silver in the central nervous system is longer than in other organs. However, the potential toxicity of silver nanoparticles (NPs) on brain tissue and the underlying mechanism(s) of action are not well understood. In this study, neurotoxicity of silver NPs was examined in rat after intragastric administration. After a two-week exposure to low-dose (1 mg/kg, body weight) or high-dose (10 mg/kg) silver NPs, the pathological and ultrastructural changes in brain tissue were evaluated with H&E staining and transmission electron microscopy. The mRNA expression levels of key tight junction proteins of the blood-brain barrier (BBB) were analyzed by real-time RT-PCR, and several inflammatory factors were assessed in blood using ELISA assay. We observed neuron shrinkage, cytoplasmic or foot swelling of astrocytes, and extra-vascular lymphocytes in silver NP exposure groups. The cadherin 1 (2(-ΔΔCt): 1.45-fold/control) and Claudin-1 (2(-ΔΔCt): 2.77-fold/control) were slightly increase in mRNA expression levels, and IL-4 significantly increased after silver NP exposure. It was suggest that silver NP can induce neuronal degeneration and astrocyte swelling, even with a low-dose (1 mg/kg) oral exposure. One potential mechanism for the effects of silver NPs to the nervous cells is involved in inflammatory effects.

In vivo analysis of dermal and systemic absorption of silver nanoparticles through healthy human skin.

BACKGROUND: Research into nanoparticles has increased markedly during the last decade, especially in light of their potential diagnostic and therapeutic use. While silver has been used since ancient times, a detailed understanding of the kinetics of its dermal absorption requires further study. Thus far, only in vitro and animal models have been used to analyse the absorption characteristics of nanocrystalline silver particles and no in vivo study using intact human skin has demonstrated silver absorption. METHOD: A nanocrystalline silver dressing was applied to a sample of 16 healthy patients with normal intact skin approximately 5 days prior to surgery. The treated skin samples, removed as surgical waste, were then analysed with a tissue mass spectrometry, light microscopy, scanning electron microscopy (SEM) and an X-ray diffusion spectrography (XRD). Silver serum levels were also analysed before and after application of the dressing. RESULTS: A limited amount of silver penetration could be noted even with light microscopy. However, definitive analysis required SEM and XRD confirmation. With SEM, metallic particles could be seen within the dermis. XRD confirmed that these were silver species, possible in oxide form. Furthermore, silver clusters as large as 750 nm could be discerned. In addition, there was no demonstrable rise in serum silver levels post-treatment with the silver dressing. CONCLUSION: Our results suggest that silver nanoparticles are able to penetrate intact human skin in vivo beyond the stratum corneum and can be found as deep as the reticular dermis. The absorbed silver might be in silver oxide form and the silver species appear to form sizeable clusters once absorbed across the epidermis. However, despite silver deposition into the dermis, the silver nanoparticles did not reach systemic circulation and should thus have no end organ consequences.

Bioenergetic failure correlates with autophagy and apoptosis in rat liver following silver nanoparticle intraperitoneal administration.

BACKGROUND: Deposition and accumulation of silver nanoparticles (Ag-nps) in the liver have been shown to induce hepatotoxicity in animal studies. The hepatotoxicity may include oxidative stress, abnormalities in energy metabolism, and cell death. Studies have indicated that autophagy is an intracellular event involving balance of energy, nutrients, and turnover of subcellular organelles. The present study was undertaken to test the hypothesis that autophagy plays a role in mediating hepatotoxicity in animal after exposure to Ag-nps. Focus was placed on interrelationship between energy metabolism, autophagy, apoptosis and hepatic dysfunction. METHODS: Sprague Dawley rats were intraperitoneally injected with Ag-nps (10-30 nm in diameter) at concentration of 500 mg kg(-1). All animals were sacrificed on days 1, 4, 7, 10 and 30 after exposure and blood and liver tissues were collected for further studies. RESULTS: Uptake of Ag-nps was quite prompt and not proportional to the blood Ag concentration. Declination of ATP (-64% in days 1) and autophagy (determined by LC3-II protein expression and morphological evaluation) increased and peaked on the first day. The ATP content remained at low level even though the autophagy has been activated. Apoptosis (based on caspase-3 protein expression and TUNEL-positive cells staining) began to rise sigmoidally at days 1 and 4, reached a peak level at day 7, and remained at the same levels during days 7-30 post exposure. Meanwhile, autophagy exhibited a gradual decrease from days 1-10 and the decrease at day 30 was statistically significant as compared to day 0 (sham group). Inflammatory reaction (histopathological evaluation) was found at day 10 and preceded to an advanced degree at day 30 when liver function was impaired. CONCLUSIONS: These results indicate that following Ag-nps administration, autophagy was induced; however, failure to preserve autophagy compounded with energy reduction led to apoptosis and the eventual impairment of liver function. The study provides an in-vivo evidence of hepatotoxicity by continuous exposure of Ag-nps in rats.

Short term serum pharmacokinetics of diammine silver fluoride after oral application.

BACKGROUND: There is growing interest in the use of diammine silver fluoride (DSF) as a topical agent to treat dentin hypersensitivity and dental caries as gauged by increasing published research from many parts of the world. While DSF has been available in various formulations for many years, most of its pharmacokinetic aspects within the therapeutic concentration range have never been fully characterized. METHODS: This preliminary study determined the applied doses (3 teeth treated), maximum serum concentrations, and time to maximum serum concentration for fluoride and silver in 6 adults over 4 h. Fluoride was determined using the indirect diffusion method with a fluoride selective electrode, and silver was determined using inductively coupled plasma-mass spectrometry. The mean amount of DSF solution applied to the 3 teeth was 7.57 mg (6.04 µL). RESULTS: Over the 4 hour observation period, the mean maximum serum concentrations were 1.86 µmol/L for fluoride and 206 nmol/L for silver. These maximums were reached 3.0 h and 2.5 h for fluoride and silver, respectively. CONCLUSIONS: Fluoride exposure was below the U.S. Environmental Protection Agency (EPA) oral reference dose. Silver exposure exceeded the EPA oral reference dose for cumulative daily exposure over a lifetime, but for occasional use was well below concentrations associated with toxicity. This preliminary study suggests that serum concentrations of fluoride and silver after topical application of DSF should pose little toxicity risk when used in adults. CLINICAL TRIALS REGISTRATION: NCT01664871.

Assessment of Silver Levels in a Closed-Incision Negative Pressure Therapy Dressing: In Vitro and In Vivo Study.

Objective: In recent years, reticulated open-cell foam-based closed-incision negative pressure therapy (ROCF-ciNPT) has shown effectiveness in management of various postoperative incisions. These dressings consist of a skin interface layer that absorbs fluid from the skin surface and reduces the potential for microbial colonization within the dressing by means of ionic silver. This study examines the ability of silver to reduce the bioburden within the dressing as well as the localized effect due to potential silver mobility. Approach: Ability of silver to reduce bioburden within the ROCF-ciNPT dressing was assessed using Staphylococcus aureus, Pseudomonas aeruginosa, and Candida spp. Furthermore, silver mobility was assessed using an in vitro skin model to study the zone of inhibition along with released silver quantification. Using a porcine model, diffusion of silver into blood and tissue was studied using emission spectrometry and histology. Results: Microbial growth in the ROCF-ciNPT dressing was significantly reduced (∼2.7-4.9 log reduction) compared to a silver-free negative control. No zone of inhibition was observed for microbial colonies for up to 7 days with minimal localized silver release (<5.5 ppm release). In vivo studies demonstrated no measurable concentration (<0.2 µg/g) of silver in the blood, urine, feces, kidney, and liver tissue biopsy. Innovation: This study provides an important insight into silver concentration and mobility within the ROCF-ciNPT dressing, given emerging concerns associated with potential silver cytotoxicity. Conclusion: These results indicate the concentration of silver (0.019% silver by weight) in the ROCF-ciNPT dressings has been adequate to reduce bioburden within the skin interface layer, while severely limiting the amount of silver leaching out.

Silver serum levels in burned patients treated with silver sulfadiazine and its toxicity on inflammatory cells.

BACKGROUND: Silver sulfadiazine (SSD) has been widely used in burned patients for the prevention of local infections. To be biologically active and exert antimicrobial properties, silver needs to be present in the form of silver ions (Ag1+) that bind to negatively charged proteins, namely, the RNA and DNA in microorganisms. However, previous published studies conducted with SSD in the 1990s reported a high level of silver absorption through damaged skin and noted the potential cytotoxicity of Ag1+ to human cells. SSD toxicity, however, had been described in cell cultures using arbitrary silver concentrations. In the present study, we determined the serum silver levels in burned patients treated with SSD and, taking into account the molar Ag1+ concentrations found in these patients, we evaluated the Ag1+ toxicity effects on inflammatory cells (ROS and cytokine production) in vitro. METHODS: Twenty patients with an average burned body surface area of 27.68% were included in this study. RESULTS: Patients' Ag1+ serum levels reached up to 558 times those of the unexposed controls. Ag1+ was then added to inflammatory cells in vitro at levels up to 2000 times the level of the control, and there was no effect on the viability of the cells nor on the rate of apoptosis. We observed a decrease in reactive oxygen species production by mononuclear (MN) and polymorphonuclear (PMN) cells, as well as a substantial decrease in cytokines IL-1ß, IL-6, IL-8, IL-10, and TNF-α production by leukocytes (MN and PNM). CONCLUSION: These findings suggest that Ag1+ may contribute to negative outcomes after burns, decreasing the primary defense mechanism (respiratory burst) and altering cytokine production.

Initial experience with silver-impregnated polyurethane ventricular catheter for shunting of cerebrospinal fluid in patients with infected hydrocephalus.

OBJECTIVE: Infection is a major complication and risk factor of cerebrospinal fluid (CSF) shunting procedures. Recently, antibiotic-impregnated shunt systems have been developed in an attempt to prevent or reduce the CSF infection. The aim of this study was to determine the efficacy of silver-impregnated polyurethane ventricular catheter for shunting of CSF in patients with infected hydrocephalus. METHODS: Seven patients who had hydrocephalus with high protein level and positive CSF culture underwent implantation of ventriculoperitoneal shunt with silver-impregnated polyurethane ventricular catheter. All of them experienced shunt failure previously due to infection. The Silverline ventricular catheter, which was connected to the Miethke gravity-assisted valve system and peritoneal catheter, was used in all patients. The mean follow-up period after operation was 14 months. Cerebrospinal fluid samples from the reservoir of the shunts were obtained at the end of the third month after operation in all patients. RESULTS: The CSF protein level of the patients was reduced significantly, and the CSF culture became negative after shunt placement with silver-impregnated polyurethane ventricular catheters. The mean CSF silver (Ag) level was 0.51 ng/ml [parts per billion (ppb)], and blood Ag level was 3.65 ng/ml (ppb) at the first month after operation. No shunt obstruction or infection was observed in the follow-up period. CONCLUSION: Silver-impregnated polyurethane ventricular catheters appear to be safe and well tolerated in patients who sustained infected hydrocephalus. Preliminary results suggest a complete improvement of infection. Longer follow-up and large number of patients are needed to more accurately assess the efficacy of these catheters.

Proteomic analysis of the bio-corona formed on the surface of (Au, Ag, Pt)-nanoparticles in human serum.

Adsorption of biomolecules onto nanoparticles surface in biological samples led to the formation of a bio-corona, it could modified the "identity" of nanoparticles, contributing to the determination of their toxicity and biocompatibility. Gel electrophoresis in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed to qualitatively analyze and identify the human serum proteins adsorbed on the surface of three different nanomaterials stabilized with citrate: 10.02 ± 0.91 nm gold nanoparticles (AuNPs), 9.73 ± 1.70 nm silver nanoparticles (AgNPs) and, 2.40 ± 0.30 nm platinum nanoparticles (PtNPs). An exhaustive analysis and classification of all identified proteins related with their function were also developed.

Induction of 8-hydroxydeoxyguanosine and ultrastructure alterations by silver nanoparticles attributing to placental transfer in pregnant rats and fetuses.

A quantitative assessment of the genotoxicity of silver nanoparticles (AgNPs) ascribed to its transplacental transfer and tissue distribution in pregnant rats was carried out in this study. A single intravenous (i.v.) injection of AgNPs with a size range from 4.0 to 17.0 nm was administered to pregnant rats at a dose of 2 mg/kg b.w. on the 19th day of gestation. Five groups beside control, each of the five rats were euthanized after 10 min, 1, 6, 12, or 24 h, respectively. The accumulation of nanoparticles (NPs) in mother and fetal tissues was quantified by inductively coupled plasma optical emission spectroscopy, where the highest accumulation level was recorded in maternal blood (0.523 µg/ml) after 24 h of administration. AgNPs induced accumulation in spleen tissue higher than placenta and fetal tissue homogenates. The data showed significantly detected levels of 8-hydroxydeoxyguanosine in all collected samples from administered animals compared with untreated individuals. Level of 8-OHdG in amniotic fluid exhibited the greatest values followed by maternal spleen, kidneys, and liver, respectively. Investigation by transmission electron microscope showed that the transfer of AgNPs through placental wall caused indentation of nuclei, clumped chromatin, pyknotic nuclei, and focal necrotic areas, while AgNPs appeared mainly accumulated in the macrophages of the spleen. Therefore, the data assume that the genotoxicity studies of AgNPs must be recommended during a comprehensive assessment of the safety of novel types of NPs and nanomaterials. Additionally, exposure to AgNPs must be prevented or minimized during pregnancy or prenatal periods.

Glucose-functionalized near-infrared Ag2Se quantum dots with renal excretion ability for long-term in vivo tumor imaging.

Non-toxic and long-term fluorescent probes for tumor imaging are in urgent need for non-invasively obtaining information about tumor genesis and metastasis in vivo. Here, we present a biocompatible near-infrared fluorescent probe for in vivo long-term imaging of tumor by modifying glucose (Glc), which experiences high uptake in cancer cells, on the surface of near-infrared Ag2Se quantum dots (NIR Ag2Se QDs). The fluorescence of glucose-functionalized Ag2Se QDs (Glc-Ag2Se QDs) from the targeted tumor can be observed in vivo for at least 7 days. In addition, this probe could be excreted through kidneys and the renal excretion ability is favorable for in vivo imaging applications. Moreover, Glc-Ag2Se QDs could be used for tumor targeted imaging of not only human breast cancer cells (MCF-7), but also SW1990 pancreatic cancer cells since glucose is highly taken up in almost all kinds of tumors. Glc-Ag2Se QDs could be a promising general tool for in vivo long-term observation of tumor evolution.