Preparation of mesoporous silica nanoparticles with different sizes and study on the correlation between size and toxicity / 药学学报

To investigate the crucial role of particle size in the biological effects of nanoparticles, a series of mesoporous silica nanoparticles (MSNs) were prepared with particle size gradients (50, 100, 150, 200 nm) with the traditional Stober method and adjusting the type and ratio of the silica source. The correlation between toxicity and size-caused biological effects were then further examined both in vitro and in vivo. The results indicated that the prepared MSNs had a uniform size, good dispersal, and ordered mesoporous structure. Hemolytic toxicity was found to be independent of particle size. At the cellular level, MSNs with smaller particle sizes were more readily internalized by cells, which initiated to more intense oxidative stress, therefor inducing higher cytotoxicity, and apoptosis rate. In vivo studies demonstrated that MSNs primarily accumulated in the liver and kidneys of mice. Pharmacokinetic analysis revealed that larger MSNs were eliminated more efficiently by the urinary system than smaller MSNs. The mice's body weight monitoring, blood tests, and pathological sections of major organs indicated good biocompatibility for MSNs of different sizes. Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Zhejiang Chinese Medical University. Overall, this study prepared MSNs with a particle size gradient to investigate the correlation between toxicity and particle size using macrophages and endothelial cells. The study also examined the biosafety of MSNs with different particle sizes in vivo and in vitro, which could help to improve the safety design strategy of MSNs for drug delivery systems.

Synthesis and evaluation of toxicity and antimicrobial activity of rifampicin associated with iron oxide nanoparticles

Rifampicin has broad-spectrum antimicrobial activity, but it can cause nephrotoxic and hepatotoxic damage because high doses are required. Nanosystems emerge as a perspective to improve the transport systems of this drug. In this work, iron oxide nanoparticles were synthesised, functionalized with lauric acid, and rifampicin was incorporated into the nanosystem. The samples were characterized by spectroscopic techniques: electronics in the visible ultraviolet region (UV-vis), vibrational absorption in the infrared region (IR), X-ray diffractometry (XRD), and dynamic light scattering (DSL). The toxicity of the nanocompounds and the antimicrobial activity against Staphylococcus aureus ATCC 25923 were studied by the Artemia salina lethality and disc diffusion techniques, respectively. As a result, IR analysis showed characteristic vibrations of laurate and rifampicin on the surface of the nanosystem. The presence of magnetic iron oxide was confirmed by XRD and the mean diameter of the crystallites was 8.37 nm. The hydrodynamic diameter of rifampicin associated with the nanosystem was 402 nm and that of the nanosystem without rifampicin was 57 nm. The compounds did not show toxicity to Artemia salina and the in vitro antimicrobial activity against Staphylococcus aureus was slightly decreased when rifampicin was associated with the nanosystem. In general terms, the results showed that iron oxide nanoparticles showed no toxicity and reduced the toxicity of rifampicin by 41.54% when carried compared to free rifampicin. Therefore, magnetic iron oxide nanoparticles may have the potential to act as a platform for associated drugs.

Renal histological alterations induced by acute exposure of titanium dioxide nanoparticles / Alteraciones histológicas renales inducidas por la exposición aguda de nanopartículas de dióxido de titanio

SUMMARY: Titanium dioxide nanoparticles (TiO2 NPs) are widely used in many commercial products, nanomedicine, agriculture, personal care products, different industries and pharmaceutical preparations with potential risk in human health and the environment. The current work was conducted to investigate the renal damage that might be induced by the acute toxicity TiO2 NPs. A total of 40 healthy male adult Wistar albino rats (Rattus norvegicus) were exposed to TiO2 NPs (126, 252, 378 mg/kg bw) for 24 and 48 h. Fresh portions of the kidneys from each rat were processed for histological and histochemical alterations. In comparison with respective control rats, exposure to TiO2 NPs has marked the following glomerular, tubular and interstitial alterations including the followings: glomerular congestion, Bowman's capsule swelling and dilatation, inflamed glomeruli, renal tubules cloudy swelling, karyorrhexis, karyolysis, infiltration of inflammatory cells, congestion, necrosis, hydropic degeneration, dilatation and congestion of blood vessels, hyaline droplets and hyaline casts precipitation, interstitial edema and fibrosis. From the findings of the current work one may conclude that TiO2 NPs are capable of inducing kidney damage with more insulation in the cortex and the proximal convoluted tubules than the medulla and the distal ones respectively. In addition, it might be concluded that renal damage induced by these nanomaterials is dose and duration of exposure dependent. Further hematological, biochemical, immunohistochemical, and ultra-structural studies are recommended.

RESUMEN: Las nanopartículas de dióxido de titanio (TiO2 NP) se usan ampliamente en muchos productos comerciales, nanomedicina, agricultura, productos para el cuidado personal, diferentes industrias y preparaciones farmacéuticas con riesgo potencial para la salud humana y el medio ambiente. El trabajo actual se realizó para investigar el daño renal que podría ser inducido por la toxicidad aguda NP de TiO2. Un total de 40 ratas Wistar albinas adultas sanas (Rattus norvegicus) fueron expuestas a TiO2 NP (126, 252, 378 mg / kg de peso corporal) durante 24 y 48 h. Las muestras de los riñones de las ratas se procesaron para estudios histológicos e histoquímicos. En comparación con las ratas control, la exposición de las ratas a TiO2 NP presentaron las siguientes alteraciones glomerulares, tubulares e intersticiales: congestión glomerular, dilatación de la cápsula de Bowman, inflamación glomerular, túbulos renales aumentados, cariorrexis, cariólisis, infiltración de células inflamatorias, congestión, necrosis, degeneración hidrópica, dilatación y congestión de vasos sanguíneos, gotas y precipitaciones hialina, edema intersticial y fibrosis. A partir de los hallazgos del trabajo actual, se puede concluir que las NP de TiO 2 son capaces de inducir daño renal con más aislamiento en la corteza y en los túbulos contorneados proximales que en la médula y los túbulos contorneados distales, respectivamente. Además, se podría concluir que el daño renal inducido por estos nanomateriales depende de la dosis y la duración de la exposición. Se recomiendan estudios adicionales hematológicos, bioquímicos, inmunohistoquímicos y ultraestructurales.

Biosynthesis of gold nanoparticles by two bacterial and fungal strains, Bacillus cereus and Fusarium oxysporum, and assessment and comparison of their nanotoxicity in vitro by direct and indirect assays

Background: Although nanoparticles (NPs) have many advantages, it has been proved that they may be absorbed by and have toxic effects on the human body. Recent research has tried to evaluate and compare the nanotoxicity of gold nanoparticles (AuNPs) produced by two types of microorganisms in vitro by two different methods. AuNPs were produced by Bacillus cereus and Fusarium oxysporum, and their production was confirmed by visible spectral, transmission electron microscope, and X-ray diffraction (XRD) analyses. The human fibroblast cell line CIRC-HLF was treated with AuNPs, and the induced nanotoxicity was measured using direct microscopic and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Results: The results showed that the produced AuNPs had a maximum absorbance peak around 510­530 nanometer (nm), with spherical, hexagonal, and octagonal shapes and average sizes around 20­50 nm. The XRD results confirmed the presence of GNPs in the microbial culture supernatants. An MTT assay showed that GNPs had dose-dependent toxic effects, and microscopic analysis showed that GNPs induced cell abnormalities in doses lower than the determined half-maximal inhibitory concentrations (IC50s). Conclusions: In conclusion, the biologically produced AuNPs had toxic effects in the cell culture, and direct techniques such as microscopic evaluation instead of indirect methods such as MTT assay were more useful for assessing the nanotoxicity of the biologically produced AuNPs. Thus, the use of only MTT assay for nanotoxicity evaluation of AuNPs is not desirable.

Cobalt oxide nanoparticles aggravate DNA damage and cell death in eggplant via mitochondrial swelling and NO signaling pathway

BACKGROUND: Despite manifold benefits of nanoparticles (NPs), less information on the risks of NPs to human health and environment has been studied. Cobalt oxide nanoparticles (Co3O4-NPs) have been reported to cause toxicity in several organisms. In this study, we have investigated the role of Co3O4-NPs in inducing phytotoxicity, cellular DNA damage and apoptosis in eggplant (Solanum melongena L. cv. Violetta lunga 2). To the best of our knowledge, this is the first report on Co3O4-NPs showing phytotoxicity in eggplant. RESULTS: The data revealed that eggplant seeds treated with Co3O4-NPs for 2 h at a concentration of 1.0 mg/ml retarded root length by 81.5 % upon 7 days incubation in a moist chamber. Ultrastructural analysis by transmission electron microscopy (TEM) demonstrated the uptake and translocation of Co3O4-NPs into the cytoplasm. Intracellular presence of Co3O4-NPs triggered subcellular changes such as degeneration of mitochondrial cristae, abundance of peroxisomes and excessive vacuolization. Flow cytometric analysis of Co3O4-NPs (1.0 mg/ml) treated root protoplasts revealed 157, 282 and 178 % increase in reactive oxygen species (ROS), membrane potential (APm) and nitric oxide (NO), respectively. Besides, the esterase activity in treated protoplasts was also found compromised. About 2.4-fold greater level of DNA damage, as compared to untreated control was observed in Comet assay, and 73.2 % of Co3O4-NPs treated cells appeared apoptotic in flow cytometry based cell cycle analysis. CONCLUSION: This study demonstrate the phytotoxic potential of Co3O4-NPs in terms of reduction in seed germination, root growth, greater level of DNA and mitochondrial damage, oxidative stress and cell death in eggplant. The data generated from this study will provide a strong background to draw attention on Co3O4-NPs environmental hazards to vegetable crops.

Nanoimaging in cardiovascular diseases: Current state of the art.

Nanotechnology has been integrated into healthcare system in terms of diagnosis as well as therapy. The massive impact of imaging nanotechnology has a deeper intervention in cardiology i.e. as contrast agents , to target vulnerable plaques with site specificity and in a theranostic approach to treat these plaques, stem cell delivery in necrotic myocardium, etc. Thus cardiovascular nanoimaging is not limited to simple diagnosis but also can help real time tracking during therapy as well as surgery. The present review provides a comprehensive description of the molecular imaging techniques for cardiovascular diseases with the help of nanotechnology and the potential clinical implications of nanotechnology for future applications.

Distribution and accumulation of 177Lu-labeled thermally cross-linked superparamagnetic iron oxide nanoparticles in the tissues of ICR mice / 대한수의학회지

To investigate kinetics of free 177Lu and 177Lu-labeled thermally cross-linked superparamagnetic iron oxide nanoparticles (TCL-SPION), suspensions were intravenously injected into the tail vein of mice at a dose of 5 microCi/mouse or 15 mg/kg body weight, respectively. Free 177Lu radioactivity levels were highest in kidney followed by liver and lung 1 day post-injection. 177Lu-labeled TCL-SPION radioactivity in liver and spleen was significantly higher compared to that of other organs throughout the experimental period (p < 0.05). Radioactivity in blood, brain, and epididymis rapidly declined until 28 days. Based on these results, TCL-SPION could be a safe carrier of therapeutics.

Size-dependent toxicity of silver nanoparticles to Glyptotendipes tokunagai

OBJECTIVES: This study aims to evaluate the size-dependent toxicity of spherical silver nanoparticles (Ag NPs) to an endemic benthic organism, Glyptotendipes tokunagai. METHODS: Ag nanoparticles of three nominal sizes (50, 100, and 150 nm) capped with polyvinyl pyrrolidone (PVP-Ag NPs) were used. Their physicochemical properties, acute toxicity (48 hours), and bioaccumulation were measured using third instar larvae of G. tokunagai. RESULTS: The aggregation and dissolution of PVP-Ag NPs increased with exposure time and concentration, respectively, particularly for 50 nm PVP-Ag NPs. However, the dissolved concentration of Ag ions was not significant compared with the median lethal concentration value for AgNO3 (3.51 mg/L). The acute toxicity of PVP-Ag NPs was highest for the smallest particles (50 nm), whereas bioaccumulation was greatest for the largest particles (150 nm). However, larger PVP-Ag NPs were absorbed and excreted rapidly, resulting in shorter stays in G. tokunagai than the smaller ones. CONCLUSIONS: The size of PVP-Ag NPs significantly affects their acute toxicity to G. tokunagai. In particular, smaller PVP-Ag NPs have a higher solubility and stay longer in the body of G. tokunagai, resulting in higher toxicity than larger PVP-Ag NPs.

Size-dependent toxicity of silver nanoparticles to Glyptotendipes tokunagai

OBJECTIVES: This study aims to evaluate the size-dependent toxicity of spherical silver nanoparticles (Ag NPs) to an endemic benthic organism, Glyptotendipes tokunagai. METHODS: Ag nanoparticles of three nominal sizes (50, 100, and 150 nm) capped with polyvinyl pyrrolidone (PVP-Ag NPs) were used. Their physicochemical properties, acute toxicity (48 hours), and bioaccumulation were measured using third instar larvae of G. tokunagai. RESULTS: The aggregation and dissolution of PVP-Ag NPs increased with exposure time and concentration, respectively, particularly for 50 nm PVP-Ag NPs. However, the dissolved concentration of Ag ions was not significant compared with the median lethal concentration value for AgNO3 (3.51 mg/L). The acute toxicity of PVP-Ag NPs was highest for the smallest particles (50 nm), whereas bioaccumulation was greatest for the largest particles (150 nm). However, larger PVP-Ag NPs were absorbed and excreted rapidly, resulting in shorter stays in G. tokunagai than the smaller ones. CONCLUSIONS: The size of PVP-Ag NPs significantly affects their acute toxicity to G. tokunagai. In particular, smaller PVP-Ag NPs have a higher solubility and stay longer in the body of G. tokunagai, resulting in higher toxicity than larger PVP-Ag NPs.

Biochemical Changes Induced by the Toxicity of Variable Sizes of Silver Nanoparticles.

Background: Silver nanoparticles (SNPs) rapid involvement in industry and nanomedicine increased human exposure to variable forms of these particles, with possible potential risk on human health. Aims: The aim of this study is to investigate the biochemical changes induced by variable sizes of SNPs toxicity. Place and Duration of Study: Faculty of Medicine, The University of Jordan and the College of Applied Medical Sciences at Aljouf University, Saudi Arabia, between January 2013 and January 2014. Study Design: Forty-two male mice were subjected to a daily single dose (1mg/kg body weight) of SNPs using five different sizes (10 nm, 20 nm, 40 nm, 60 nm and 100 nm) for 35 days. Methodology: Biochemical changes of the following eleven biochemical tests were determined: aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, triglycerides, total bilirubin, creatinine, total protein, albumin, urea, uric acid and total cholesterol. Results: Silver nanoparticles significantly elevated aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, triglycerides, total bilirubin and creatinine, with no significant change in total protein level while albumin and total cholesterol levels were lowered. Conclusion: The findings indicate that exposure to SNPs produced significant biochemical changes that might affect the functions of the vital organs. Moreover, these alterations were size-dependent with smaller particles (10 nm and 20 nm) induced more alterations than the larger ones.

The Risk Evaluation of Tungsten Oxide Nanoparticles in Cultured Rat Liver Cells for Its Safe Applications in Nanotechnology

Tungsten (VI) oxide (WO3) nanoparticles (NPs) are used for many industrial purposes in everyday life. However, their effects on human health have not been sufficiently evaluated. Therefore, the present study was designed to investigate the toxicity potentials of various concentrations (0 to 1000 ppm) of WO3 NPs (<100 nm particle size) in cultured primary rat hepatocytes. The results of cell viability assay showed that the higher concentrations of dispersed WO3 NPs (300, 500 and 1000 ppm) caused significant (p<0.05) decreases of cell viability. Also, dose dependent negative alterations were observed in oxidative status and antioxidant capacity levels after the application of WO3 in cultured rat primary hepatocytes. The results of genotoxicity tests revealed that these NPs did not cause significant increases of micronucleated hepatocytes (MNHEPs) but increased 8-oxo-2-deoxyguanosine (8-OH-dG) levels as compared to the control culture.

Physical damage -the origin of nanotoxicity / 中国药理学与毒理学杂志

Despite tre mendous research efforts have been devoted to the analysis of nanoparticles (NPs)biohazard,the potential mechanism for nanotoxicity has not yet been syste mati-cal y elucidated.This review intends to point out the confusions about nanotoxicity in the field and tries to look into the mecha-nism from a new perspective.Currently,there are three puzzles:① no relationship between dose and toxicity could be observed in nanotoxicity;②there is a theory for the″size effects″,however, it cannot explain some cases contrary to the doctrine;③ NPs made of different materials with various sizes could have the same toxic effects through sti mulating oxidative stress.In fact, human body is co mposed of various biological molecules,and the biological function of a living syste m is reflected by the inter-actions and conversions of those molecules.NPs,on the other hand,are the invader of human body which has no ability to transport or convert or digest the foreigner.Thus,NPs could cause celldamage due to the physical blockage of micro-circula-tion,celldestruction due to membrane rando m insertion,and celldysfunction due to physical contacting with big biological mole-cules.The physical damages caused by various NPs could be divided into three categories:adhesion lesion,card inlay and puncture.Above al ,by analyzing wide spectrum of NPs varying in co mposition,shape and size,the author draws a conclusion that physical damage is the origin of nanotoxicity.

Nanomaterials and Nanotoxicity in the Present Scenario: A Short Review.

Nanomaterials have begun to play an integral part of our daily life as they are being increasingly used in medicines, prosthetics, engineering materials, house hold articles, clothes, paints, etc,. At present there are few studies about the hazards of nanoparticles to human health. Ecotoxicological issues due to nanomaterials have received even less attention, which is alarming since production of nanomaterials is progressing at a brisk scale. This review addresses some of the health concerns pertaining to nanomaterials in the light of their tremendous potential for extensive use in various fields.

Studying nanotoxic effects of CdTe quantum dots in Trypanosoma cruzi

Semiconductor nanoparticles, such as quantum dots (QDs), were used to carry out experiments in vivo and ex vivo with Trypanosoma cruzi. However, questions have been raised regarding the nanotoxicity of QDs in living cells, microorganisms, tissues and whole animals. The objective of this paper was to conduct a QD nanotoxicity study on living T. cruzi protozoa using analytical methods. This was accomplished using in vitro experiments to test the interference of the QDs on parasite development, morphology and viability. Our results show that after 72 h, a 200 μM cadmium telluride (CdTe) QD solution induced important morphological alterations in T. cruzi, such as DNA damage, plasma membrane blebbing and mitochondrial swelling. Flow cytometry assays showed no damage to the plasma membrane when incubated with 200 μM CdTe QDs for up to 72 h (propidium iodide cells), giving no evidence of classical necrosis. Parasites incubated with 2 μM CdTe QDs still proliferated after seven days. In summary, a low concentration of CdTe QDs (2 μM) is optimal for bioimaging, whereas a high concentration (200 μM CdTe) could be toxic to cells. Taken together, our data indicate that 2 μM QD can be used for the successful long-term study of the parasite-vector interaction in real time.