An affibody-conjugated nanoprobe for IGF-1R targeted cancer fluorescent and photoacoustic dual-modality imaging.

Dual-modal molecular imaging that combines photoacoustic imaging with near-infrared fluorescence imaging integrates the benefits of both imaging modalities and may achieve more precise detection of disease. In this study, silver sulfide quantum dots (Ag2S QDs) with superior photoacoustic properties and a strong fluorescent emission in the NIR region were successfully synthesized. They were further modified with the insulin-like growth factor 1 receptor (IGF-1R) targeted small scaffold protein, Affibody (ZIGF-1) to achieved targeted photoacoustic/fluorescent dual-modal imaging of cancer. Our results showed that the prepared nanoprobe had good tumor targeting properties in vivo, and the probe also showed good biocompatibility without any significant toxicity.

Ag2[Fe(CN)5NO]-Fabricated Hydrophobic Cotton as a Potential Wound Healing Dressing: An In Vivo Approach.

There have been reports of different types of wound dressings for various functions and purposes. Cotton being one of the most widely used wound dressing material due to its non-toxic, biodegradable, and other properties is used for fabrication as well as in the form of scaffolds for faster and effective wound closure. Our research team has already demonstrated the role of silver nitroprusside nanoparticles (SNPNPs) for wound healing and antibacterial activity. In the current study, we have developed cotton fabric impregnated with SNPNPs (SNPCFs) which remain photo inert and displayed long-term antimicrobial activity due to the surface modification with the silver nitroprusside complex. These SNPCFs were characterized by various analytical techniques (XRD, FTIR, UV spectroscopy, TGA, TEM, FESEM, EDAX, ICP-OES). The fabricated cotton dressings with nanoparticles showed an improved water contact angle (113-130°) than that of bare cotton gauze (60°) and exhibited more antibacterial property in case of both Gram-negative bacteria (Klebsiella aerogenes and Escherichia coli) and Gram-positive bacteria (Pseudomonas aeruginosa and Bacillus subtilis) even after several washings. The biocompatible nature of SNPCFs was assessed by in vivo chorioallantoic membrane assay that showed no obstruction in the formation of blood vessels. The SNPCFs exhibited better wound healing activity compared to the bare cotton and AgCFs as observed in the C57BL6/J mouse. The histopathological investigation reveals increase in re-epithelialization and deposition of connective tissue. The macrophage (M2) counts in SNPCF-treated skin tissues were supportive of more wound healing activity than mice treated with cotton fabric impregnated with chemically synthesized silver nanoparticles. Based on biodistribution analysis using ICP-OES, the data illustrated that a significant amount of silver is absorbed in the skin tissues of mice as compared to the blood and kidney. Furthermore, the absence of silver from the vital organs (heart, liver, and kidney) corroborates our hypothesis that the SNPCFs can act excellently in treating wounds when topically applied over skin. Thereafter, all these results highlight a strong possibility that SNPCFs exemplify the potential as a new antimicrobial and wound healing agent in future times.

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.

Pharmacokinetics, Tissue Distribution and Excretion of Ag2S Quantum Dots in Mice and Rats: the Effects of Injection Dose, Particle Size and Surface Charge.

PURPOSE: We systematically investigated the effects of injection dose, particle size and surface charge on the pharmacokinetics, tissue distribution and excretion of Ag2S quantum dots (Qds) in rats and mice. METHODS: Three different doses of Ag2S Qds with similar size and composition were administrated to rats and mice. The effect of size and surface charge was investigated with the injection of three sizes (5, 15 and 25 nm) of Ag2S Qds possessing similar surface charge, as well as 5 nm Qds with a positive surface charge. RESULTS: Results indicated that pharmacokinetics and biodistribution of Ag2S Qds were strongly dose, particle size and surface charge dependent. By increasing the dose from 0.5 to 4.0 mg/kg, mean residence time (MRT) and apparent volume of distribution at steady state (Vss) were increased while clearance (CL) was decreased. Qds with a negative surface charge had significantly larger MRT and Vss values than positively charged particles, but their CL was about 50% lower than that of positively charged ones. By increasing Qds size from 5 to 25 nm, CL was increased while MRT and AUC were decreased. CONCLUSIONS: This study establishes comprehensive principles for the rational design and tailoring of Ag2S Qds for biomedical applications. Graphical Abstract The effects of injection dose, particle size and surface charge on pharmacokinetics and tissue distribution of Ag2S Qds after intravenous injection into rats and mice were investigated.

Ultrafast synthesis of ultrasmall polyethylenimine-protected AgBiS2 nanodots by "rookie method" for in vivo dual-modal CT/PA imaging and simultaneous photothermal therapy.

Developing a biocompatible nanotheranostic platform integrating diagnostic and therapeutic functions is a great prospect for cancer treatment. However, it is still a great challenge to synthesize nanotheranostic agents using an ultra-facile method. In the research reported here, ultrasmall polyethylenimine-protected silver bismuth sulfide (PEI-AgBiS2) nanodots were successfully synthesized using an ultra-facile and environmentally friendly strategy (1 min only at room temperature), which could be described as a "rookie method". PEI-AgBiS2 nanodots show good monodispersity and biocompatibility. For the first time, PEI-AgBiS2 nanodots were reported as a powerful and safe nanotheranostic agent for cancer treatment. PEI-AgBiS2 nanodots exhibit excellent computed tomography (CT) and photoacoustic (PA) dual-modal imaging ability, which could effectively guide photothermal cancer therapy. Furthermore, PEI-AgBiS2 nanodots exhibit a high photothermal conversion efficiency (η = 35.2%). The photothermal therapy (PTT) results demonstrated a highly efficient tumor ablation ability. More importantly, the blood biochemistry and histology analyses verify that the PEI-AgBiS2 nanodots have negligible long-term toxicity. This work highlights that PEI-AgBiS2 nanodots produced using this extremely effective method are a high-performance and safe PTT agent. These findings open a new gateway for synthesizing nanotheranostic agents by using this ultra-facile method in the future.

The effect of chronic silver nanoparticles on aquatic system in microcosms.

Silver nanoparticles (AgNPs) inevitably discharge into aquatic environments due to their abundant use in antibacterial products. It was reported that in laboratory conditions, AgNPs display dose-dependent toxicity to aquatic organisms, such as bacteria, algae, macrophytes, snails and fishes. However, AgNPs could behave differently in natural complex environments. In the present study, a series of microcosms were established to investigate the distribution and toxicity of AgNPs at approximately 500 µg L-1 in aquatic systems. As a comparison, the distribution and toxicity of the same concentration of AgNO3 were also determined. The results showed that the surface layer of sediment was the main sink of Ag element for both AgNPs and AgNO3. Both aquatic plant (Hydrilla verticillata) and animals (Gambusia affinis and Radix spp) significantly accumulated Ag. With short-term treatment, phytoplankton biomass was affected by AgNO3 but not by AgNPs. Chlorophyll content of H. verticillata increased with both AgNPs and AgNO3 short-term exposure. However, the biomass of phytoplankton, aquatic plant and animals was not significantly different between control and samples treated with AgNPs or AgNO3 for 90 d. The communities, diversity and richness of microbes were not significantly affected by AgNPs and AgNO3; in contrast, the nitrification rate and its related microbe (Nitrospira) abundance significantly decreased. AgNPs and AgNO3 may affect the nitrogen cycle and affect the environment and, since they might be also transferred to food web, they represent a risk for health.

Engineered Multifunctional Nanomedicine for Simultaneous Stereotactic Chemotherapy and Inhibited Osteolysis in an Orthotopic Model of Bone Metastasis.

A novel multifunctional Ag2 S quantum dot (QD)-based nanomedicine of alendronate (Ald)/doxorubicin (DOX)@Ag2 S is developed for highly effective bone tumor therapy in an orthotopic model. The bone-targeting and osteolysis inhibition of Ald and the chemotherapeutic effect of DOX on the bone tumor are in situ visualized by Ag2 S QDs with emission in the second near-infrared window.

Disposition of intravenously or orally administered silver nanoparticles in pregnant rats and the effect on the biochemical profile in urine.

Few investigations have been conducted on the disposition and fate of silver nanoparticles (AgNP) in pregnancy. The distribution of a single dose of polyvinylpyrrolidone (PVP)-stabilized AgNP was investigated in pregnant rats. Two sizes of AgNP, 20 and 110 nm, and silver acetate (AgAc) were used to investigate the role of AgNP diameter and particle dissolution in tissue distribution, internal dose and persistence. Dams were administered AgNP or AgAc intravenously (i.v.) (1 mg kg-1 ) or by gavage (p.o.) (10 mg kg-1 ), or vehicle alone, on gestation day 18 and euthanized at 24 or 48 h post-exposure. The silver concentration in tissues was measured using inductively-coupled plasma mass spectrometry. The distribution of silver in dams was influenced by route of administration and AgNP size. The highest concentration of silver (µg Ag g-1 tissue) at 48 h was found in the spleen for i.v. administered AgNP, and in the lungs for AgAc. At 48 h after p.o. administration of AgNP, the highest concentration was measured in the cecum and large intestine, and for AgAc in the placenta. Silver was detected in placenta and fetuses for all groups. Markers of cardiovascular injury, oxidative stress marker, cytokines and chemokines were not significantly elevated in exposed dams compared to vehicle-dosed control. NMR metabolomics analysis of urine indicated that AgNP and AgAc exposure impact the carbohydrate, and amino acid metabolism. This study demonstrates that silver crosses the placenta and is transferred to the fetus regardless of the form of silver. Copyright © 2016 John Wiley & Sons, Ltd.

Direct Synthesis of Water-Soluble Aptamer-Ag2 S Quantum Dots at Ambient Temperature for Specific Imaging and Photothermal Therapy of Cancer.

Water-soluble Ag2 S near-infrared (NIR) fluorescent quantum dots (QDs) are directly synthesized at ambient temperature for specific cancer imaging and photothermal therapy (PTT) using a designed aptamer (Apt43) as template, which consists of the following two fragments: an aptamer S2.2 sequence for specifically recognizing the cancer cells and an 18-cytosine (18-C) extending spacer for growing Ag2 S QDs. The synthesized Ag2 S QDs (Apt43-Ag2 S QDs), which exhibit strong absorption and fluorescence emission in the NIR region and high photothermal conversion capabilities, can specifically recognize MCF-7 cells (human breast cancer cells) and are usable as a highly intensified imaging agent for cancer diagnosis. Moreover, they can be applied as photothermal agents for the in vitro killing of MCF-7 cells and the in vivo ablation of tumors, which were constructed on the bodies of nude mice. MCF-7 cells almost quantitatively die after they are incubated with the QDs (at 100 µg mL(-1) ) for 2 h and irradiated under an 808 nm laser at a power density of 1.0 W cm(-2) for 10 min. The tumors on the nude mice can also be effectively ablated without regrowth during the period of observation (at least 20 d) after PTT.

Blood Clearance, Distribution, Transformation, Excretion, and Toxicity of Near-Infrared Quantum Dots Ag2Se in Mice.

As a novel fluorescent probe in the second near-infrared window, Ag2Se quantum dots (QDs) exhibit great prospect in in vivo imaging due to their maximal penetration depth and negligible background. However, the in vivo behavior and toxicity of Ag2Se QDs still largely remain unknown, which severely hinders their wide-ranging biomedical applications. Herein, we systematically studied the blood clearance, distribution, transformation, excretion, and toxicity of polyethylene glycol (PEG) coated Ag2Se QDs in mice after intravenous administration with a high dose of 8 µmol/kg body weight. QDs are quickly cleared from the blood with a circulation half-life of 0.4 h. QDs mainly accumulate in liver and spleen and are remarkably transformed into Ag and Se within 1 week. Ag is excreted from the body readily through both feces and urine, whereas Se is excreted hardly. The toxicological evaluations demonstrate that there is no overt acute toxicity of Ag2Se QDs to mice. Moreover, in regard to the in vivo stability problem of Ag2Se QDs, the biotransformation and its related metabolism are intensively discussed, and some promising coating means for Ag2Se QDs to avert transformation are proposed as well. Our work lays a solid foundation for safe applications of Ag2Se QDs in bioimaging in the future.

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.

Effects of particle size and coating on toxicologic parameters, fecal elimination kinetics and tissue distribution of acutely ingested silver nanoparticles in a mouse model.

Consumer exposure to silver nanoparticles (AgNP) via ingestion can occur due to incorporation of AgNP into products such as food containers and dietary supplements. AgNP variations in size and coating may affect toxicity, elimination kinetics or tissue distribution. Here, we directly compared acute administration of AgNP of two differing coatings and sizes to mice, using doses of 0.1, 1 and 10 mg/kg body weight/day administered by oral gavage for 3 days. The maximal dose is equivalent to 2000× the EPA oral reference dose. Silver acetate at the same doses was used as ionic silver control. We found no toxicity and no significant tissue accumulation. Additionally, no toxicity was seen when AgNP were dosed concurrently with a broad-spectrum antibiotic. Between 70.5% and 98.6% of the administered silver dose was recovered in feces and particle size and coating differences did not significantly influence fecal silver. Peak fecal silver was detected between 6- and 9-h post-administration and <0.5% of the administered dose was cumulatively detected in liver, spleen, intestines or urine at 48 h. Although particle size and coating did not affect tissue accumulation, silver was detected in liver, spleen and kidney of mice administered ionic silver at marginally higher levels than those administered AgNP, suggesting that silver ion may be more bioavailable. Our results suggest that, irrespective of particle size and coating, acute oral exposure to AgNP at doses relevant to potential human exposure is associated with predominantly fecal elimination and is not associated with accumulation in tissue or toxicity.

Toxicity of nanosilver in intragastric studies: Biodistribution and metabolic effects.

The unique physicochemical properties of silver nanoparticles explain their extensive application in consumer goods, food, and medicinal products. However, the biological effects of nanosilver after peroral exposure of mammals are still debatable. This study describes the biodistribution and biological action of 12nm non-coated silver nanoparticles intragastrically administered to male rats after acute (single exposure) and sub-acute (multiple exposures over 30 days) toxicity experiments. The daily doses were 2000 and 250mg/kg of body weight for single and multiple administrations, respectively. Silver tissue detection was conducted by elemental analysis with the help of atomic absorption spectroscopy. An estimation of the state of exposed animals was made and the dynamics of hematological and biochemical parameters of rats was studied. It was demonstrated that single and multiple administrations resulted in silver accumulation in the liver, kidneys, spleen, stomach, and small intestine. After both one- and repeated-dose exposures, the highest Ag contents were detected in the liver (0.87±0.37µg/g of organ) and kidneys (0.24±0.02µg/g of organ). The concentrations of silver detected in tissues were far smaller than the administered doses (<99%), indicating its efficient excretion from the organism. Acute and sub-acute exposures caused no animal mortality or signs of toxicity, manifested as changes in outward appearance or notable deviations in behavior or locomotor activity. Postmortem study revealed no visible pathomorphological abnormalities of internal organs. Hematological indices and biochemical parameters of the treated rats did not differ from those of the vehicle control animals. Overall, it can be concluded that nanosilver is able to be absorbed from the gastrointestinal tract into the bloodstream and accumulate in the secondary organs of rats. It showed no distinct toxicity under the experimental conditions of this study.

In vivo cancer targeting and fluorescence-CT dual-mode imaging with nanoprobes based on silver sulfide quantum dots and iodinated oil.

In this article, a fluorescence-CT dual-mode nanoprobe is successfully synthesized by making use of distearoylphosphatidylethanolamine-poly(ethylene glycol)-folate (DSPE-PEG2000-FA) and other amphiphilic molecules to coat silver sulfide (Ag2S) quantum dots (QDs) and iodinated oil simultaneously. In vitro experiments show that the fluorescence wavelength of the nanoprobe is 1170 nm in the near infrared-II region. Its size is 139.6 nm, it has good dispersibility, and it has low cellular toxicity at concentrations up to 25 µg mL(-1) Ag. In vivo experiments revealed that the probe has a rather long circulation time (blood half-life of 5.7 hours), and the tissue histopathological tests show that it is not obviously harmful to major organs' normal function. Biochemical analysis (glutamic pyruvic transaminase and glutamic oxaloacetic transaminase levels) and blood analysis (white blood cell, red blood cell, hemoglobin and blood platelet counts) reveal that it has little influence on blood within 15 days of administration. When injected into HeLa xenograft nude mice by the tail vein, the probe elicited intensely enhanced fluorescence and X-ray computed tomography (CT) signals in the tumors after 24 hours, and the structure, size and position of tumor tissue were shown clearly. In a word, the probe has good tumor targeting capabilities, and it has significant value in fluorescence-CT dual-mode imaging in vivo.

[APPROACHES TO ENHANCING THE ORGANISM'S RESISTANCE TO THE ADVERSE EFFECTS OF NANOMATERIALS AS EXAMPLIFIED BY NANOSILVER AND NANOCOPPER OXIDE].

Subchronic intoxications in rats induced by repeated intraperitoneal injections of stable water suspensions of silver or copper oxide nanoparticles in low dosage were manifested by adverse shifts in some functional and biochemical indices, by development of histo-structural changes in different tissues and by poly-organ fragmentation of DNA. All these manifestations of toxicity were substantially attenuated against the background of parallel oral administration of bioprotective complexes comprising vitamins, trace elements, pectin, some amino acids and a fish oil preparation rich in omega-3 fee fatty acids, this composition has been adjusted to mechanisms of action of this or that nanomaterial.

Speciation Matters: Bioavailability of Silver and Silver Sulfide Nanoparticles to Alfalfa (Medicago sativa).

Terrestrial crops are directly exposed to silver nanoparticles (Ag-NPs) and their environmentally transformed analog silver sulfide nanoparticles (Ag2S-NPs) when wastewater treatment biosolids are applied as fertilizer to agricultural soils. This leads to a need to understand their bioavailability to plants. In the present study, the mechanisms of uptake and distribution of silver in alfalfa (Medicago sativa) were quantified and visualized upon hydroponic exposure to Ag-NPs, Ag2S-NPs, and AgNO3 at 3 mg total Ag/L. Total silver uptake was measured in dried roots and shoots, and the spatial distribution of elements was investigated using transmission electron microscopy (TEM) and synchrotron-based X-ray imaging techniques. Despite large differences in release of Ag(+) ions from the particles, Ag-NPs, Ag2S-NPs, and Ag(+) became associated with plant roots to a similar degree, and exhibited similarly limited (<1%) amounts of translocation of silver into the shoot system. X-ray fluorescence (XRF) mapping revealed differences in the distribution of Ag into roots for each treatment. Silver nanoparticles mainly accumulated in the (columella) border cells and elongation zone, whereas Ag(+) accumulated more uniformly throughout the root. In contrast, Ag2S-NPs remained largely adhered to the root exterior, and the presence of cytoplasmic nano-SixOy aggregates was observed. Exclusively in roots exposed to particulate silver, NPs smaller than the originally dosed NPs were identified by TEM in the cell walls. The apparent accumulation of Ag in the root apoplast determined by XRF, and the presence of small NPs in root cell walls suggests uptake of partially dissolved NPs and translocation along the apoplast.

Comparative toxicity of silicon dioxide, silver and iron oxide nanoparticles after repeated oral administration to rats.

Although silicon dioxide (SiO2), silver (Ag) and iron oxide (Fe2O3) nanoparticles are widely used in diverse applications from food to biomedicine, in vivo toxicities of these nanoparticles exposed via the oral route remain highly controversial. To examine the systemic toxicity of these nanoparticles, well-dispersed nanoparticles were orally administered to Sprague-Dawley rats daily over a 13-week period. Based on the results of an acute toxicity and a 14-day repeated toxicity study, 975.9, 1030.5 and 1000 mg kg(-1) were selected as the highest dose of the SiO2 , Ag and Fe2O3 nanoparticles, respectively, for the 13-week repeated oral toxicity study. The SiO2 and Fe2O3 nanoparticles did not induce dose-related changes in a number of parameters associated with the systemic toxicity up to 975.9 and 1000 mg kg(-1) , respectively, whereas the Ag nanoparticles resulted in increases in serum alkaline phosphatase and calcium as well as lymphocyte infiltration in liver and kidney, raising the possibility of liver and kidney toxicity induced by the Ag nanoparticles. Compared with the SiO2 and Fe2O3 nanoparticles showing no systemic distribution in all tissues tested, the Ag concentration in sampled blood and organs in the Ag nanoparticle-treated group significantly increased with a positive and/or dose-related trend, meaning that the systemic toxicity of the Ag nanoparticles, including liver and kidney toxicity, might be explained by extensive systemic distribution of Ag originating from the Ag nanoparticles. Our current results suggest that further study is required to identify that Ag detected outside the gastrointestinal tract were indeed a nanoparticle form or ionized form.

Silver sulfide nanoparticles (Ag2S-NPs) are taken up by plants and are phytotoxic.

Silver nanoparticles (NPs) are used in more consumer products than any other nanomaterial and their release into the environment is unavoidable. Of primary concern is the wastewater stream in which most silver NPs are transformed to silver sulfide NPs (Ag2S-NPs) before being applied to agricultural soils within biosolids. While Ag2S-NPs are assumed to be biologically inert, nothing is known of their effects on terrestrial plants. The phytotoxicity of Ag and its accumulation was examined in short-term (24 h) and longer-term (2-week) solution culture experiments with cowpea (Vigna unguiculata L. Walp.) and wheat (Triticum aestivum L.) exposed to Ag2S-NPs (0-20 mg Ag L(-1)), metallic Ag-NPs (0-1.6 mg Ag L(-1)), or ionic Ag (AgNO3; 0-0.086 mg Ag L(-1)). Although not inducing any effects during 24-h exposure, Ag2S-NPs reduced growth by up to 52% over a 2-week period. This toxicity did not result from their dissolution and release of toxic Ag(+) in the rooting medium, with soluble Ag concentrations remaining below 0.001 mg Ag L(-1). Rather, Ag accumulated as Ag2S in the root and shoot tissues when plants were exposed to Ag2S-NPs, consistent with their direct uptake. Importantly, this differed from the form of Ag present in tissues of plants exposed to AgNO3. For the first time, our findings have shown that Ag2S-NPs exert toxic effects through their direct accumulation in terrestrial plant tissues. These findings need to be considered to ensure high yield of food crops, and to avoid increasing Ag in the food chain.

Cellular uptake and toxicity effects of silver nanoparticles in mammalian kidney cells.

The rapid progress and early commercial acceptance of silver-based nanomaterials is owed to their biocidal activity. Besides embracing the antimicrobial potential of silver nanoparticles (AgNPs), it is imperative to give special attention to the potential adverse health effects of nanoparticles owing to prolonged exposure. Here, we report a detailed study on the in vitro interactions of citrate-coated AgNPs with porcine kidney (Pk15) cells. As uncertainty remains whether biological/cellular responses to AgNPs are solely as a result of the release of silver ions or whether the AgNPs themselves have toxic effects, we investigated the effects of Ag(+) on Pk15 cells for comparison. Next, we investigated the cellular uptake of both AgNPs and Ag(+) in Pk15 cells at various concentrations applied. The detected Ag contents in cells exposed to 50 mg l(-1) AgNPs and 50 mg l(-1) Ag(+) were 209 and 25 µg of Ag per 10(6) cells, respectively. Transmission electron microscopy (TEM) images indicated that the Pk15 cells internalized AgNPs by endocytosis. Both forms of silver, nano and ionic, decreased the number of viable Pk15 cells after 24 h in a dose-dependent manner. In spite of a significant uptake into the cells, AgNPs had only insignificant toxicity at concentrations lower than 25 mg l(-1) , whereas Ag(+) exhibited a significant decrease in cell viability at one-fifth of this concentration. The Comet assay suggested that a rather high concentration of AgNP (above 25 mg l(-1) ) is able to induce genotoxicity in Pk15 cells. Further studies must seek deeper understanding of AgNP behavior in biological media and their interactions with cellular membranes.