RESUMEN
Iridium(III) complexes have gained great attention in cancer treatment in recent years. In this paper, we designed and synthesized a new iridium(III) complex [Ir(piq)2(DQTT)](PF6) Ir1 (piq = 1-phenylisoquinoline, DQTT = 12-(1,4-dihydroquinoxalin-6-yl)-4,5,9,14-tetraazabenzo[b]triphenylene). The Ir1-loaded PEGylated liposomes (Lipo-Ir1) were prepared using the ethanol injection method. The anticancer activity of the complex and Lipo-Ir1 against SGC-7901 (human gastric adenocarcinoma), A549 (human lung carcinoma), HeLa (human cervical carcinoma), HepG2 (human hepatocellular carcinoma), BEL-7402 (human hepatocellular carcinoma), and normal NIH3T3 (mouse embryonic fibroblasts) was tested by the MTT method. The complex Ir1 shows moderate or low cytotoxicity against the selected cancer cells, whereas the Lipo-Ir1 exhibits high anticancer activity toward the same cancer cells. The apoptosis induced by Lipo-Ir1 was assayed by flow cytometry and Lipo-Ir1 induced apoptosis through increasing intracellular reactive-oxygen species levels, decreasing mitochondrial membrane potential, further promoting cytochrome c release and causing the increase of level of intracellular Ca2+. Western blot was used to detect the changes in Bcl-2 family protein and PI3K/AKT pathway proteins. The cloning experiments demonstrated that the Lipo-Ir1 can effectively inhibit cell proliferation. In vivo experiments, Lipo-Ir1 inhibited tumor growth in xenograft nude mice, and the percentage of tumor growth inhibition in vivo was 75.70%. Overall, the liposomes Lipo-Ir1 exhibits higher anticancer activity than Ir1 under the same conditions. These results indicated that Lipo-Ir1 may be a valuable resource for cancer therapy.
Asunto(s)
Antineoplásicos/uso terapéutico , Complejos de Coordinación/uso terapéutico , Portadores de Fármacos/química , Liposomas/química , Neoplasias/tratamiento farmacológico , Animales , Antineoplásicos/química , Antineoplásicos/toxicidad , Apoptosis/efectos de los fármacos , Calcio/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Complejos de Coordinación/química , Complejos de Coordinación/toxicidad , Portadores de Fármacos/toxicidad , Liberación de Fármacos , Hemólisis/efectos de los fármacos , Iridio/química , Iridio/toxicidad , Liposomas/toxicidad , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Mitocondrias/efectos de los fármacos , Células 3T3 NIH , Neoplasias/patología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Thiol-containing amino acids, cysteine (Cys) and homocysteine (Hcy), play crucial roles in the biosystem; their abnormal contents in the cells are linked to many diseases. Herein, we designed and synthesized a novel near-infrared (NIR) phosphorescent iridium(iii) complex-based probe (FNO1) that can detect Cys and Hcy in real-time in the biosystem. Due to the advantages of the iridium complex, the FNO1 probe had excellent chemical stability and photostability, high luminescence efficiency, and long luminescence lifetime. In addition, the probe showed a fast response, high sensitivity, and low cytotoxicity. As verified by high resolution mass spectra (HR-MS) and density functional theory (DFT) calculations, the detection was achieved through the addition of the α,ß-unsaturated ketone group in FNO1 by the nucleophilic thiol group in Cys and Hcy. Through time-resolved emission spectroscopy (TRES) and in the presence of a strongly fluorescent dye rhodamine B, the FNO1 probe could detect Cys and Hcy due to its long luminescence lifetime (260/197 ns). Finally, owing to its NIR-emitting properties, the FNO1 probe was successfully applied in the imaging of Cys and Hcy in living cells, zebrafish, and mice.
Asunto(s)
Complejos de Coordinación/química , Cisteína/análisis , Homocisteína/análisis , Sustancias Luminiscentes/química , Animales , Complejos de Coordinación/síntesis química , Complejos de Coordinación/toxicidad , Teoría Funcional de la Densidad , Humanos , Iridio/química , Iridio/toxicidad , Sustancias Luminiscentes/síntesis química , Sustancias Luminiscentes/toxicidad , Mediciones Luminiscentes , Células MCF-7 , Ratones , Microscopía Confocal , Modelos Químicos , Rodaminas/química , Pez CebraRESUMEN
BACKGROUND: Concerns have been expressed that inhaled nanoparticles may behave differently to larger particles in terms of lung clearance and translocation, with potential implications for their toxicity. Studies undertaken to investigate this have typically involved limited post-exposure periods. There is a shortage of information on longer-term clearance and translocation patterns and their dependence on particle size, which this study aimed to address. METHODS: Rats were exposed (<3 h) nose-only to aerosols of spark-generated radioactive iridium-192 nanoparticles of four sizes: 10 nm, 15 nm, 35 nm and 75 nm (count median diameter) (aerosol mass concentrations 17, 140, 430, and 690 µg/m3, respectively). The content of iridium-192 in the whole animal, organs, tissues, and excreta was measured at various times post-exposure to ≥ 1 month. Limited toxicological investigations were undertaken for the 10 nm aerosol using bronchoalveolar lavage fluid. Elemental maps of tissue samples were produced using laser ablation inductively coupled plasma mass spectrometry and synchrotron micro-focus x-ray fluorescence. The chemical speciation of the iridium was explored using synchrotron micro focus x-ray near-edge absorption spectroscopy. RESULTS: Long-term lung retention half-times of several hundred days were found, which were not dependent on particle size. There was significant variation between individual animals. Analysis of bronchoalveolar lavage fluid for the 10 nm aerosol indicated a limited inflammatory response resolving within the first 7 days. Low levels of, particle size dependent, translocation to the kidney and liver were found (maximum 0.4% of the lung content). Any translocation to the brain was below the limits of detection (i.e. < 0.01% of the lung content). The kidney content increased to approximately 30 days and then remained broadly constant or decreased, whereas the content in the liver increased throughout the study. Laser ablation inductively coupled plasma mass spectrometry analysis indicated homogeneous iridium distribution in the liver and within the cortex in the kidney. CONCLUSIONS: Slow lung clearance and a pattern of temporally increasing concentrations in key secondary target organs has been demonstrated for inhaled iridium aerosol particles < 100 nm, which may have implications for long-term toxicity, especially in the context of chronic exposures.
Asunto(s)
Iridio/farmacocinética , Pulmón/metabolismo , Nanopartículas del Metal/química , Aerosoles , Animales , Transporte Biológico , Líquido del Lavado Bronquioalveolar/química , Supervivencia Celular/efectos de los fármacos , Femenino , Exposición por Inhalación , Iridio/química , Iridio/toxicidad , Tasa de Depuración Metabólica , Nanopartículas del Metal/toxicidad , Especificidad de Órganos , Tamaño de la Partícula , Ratas Endogámicas WKY , Distribución TisularRESUMEN
BACKGROUND: Persons with cystic fibrosis (CF) are at-risk for health effects from ambient air pollution but little is known about the interaction of nanoparticles (NP) with CF lungs. Here we study the distribution of inhaled NP in a murine CF model and aim to reveal mechanisms contributing to adverse effects of inhaled particles in susceptible populations. METHODS: Chloride channel defective CftrTgH (neoim) Hgu mice were used to analyze lung function, lung distribution and whole body biokinetics of inhaled NP, and inflammatory responses after intratracheal administration of NP. Distribution of 20-nm titanium dioxide NP in lungs was assessed on ultrathin sections immediately and 24 h after a one-hour NP inhalation. NP biokinetics was deduced from total and regional lung deposition and from whole body translocation of inhaled 30-nm iridium NP within 24 h after aerosol inhalation. Inflammatory responses were assessed within 7 days after carbon NP instillation. RESULTS: Cftr mutant females had moderately reduced lung compliance and slightly increased airway resistance compared to wild type mice. We found no genotype dependent differences in total, regional and head deposition or in secondary-organ translocation of inhaled iridium NP. Titanium dioxide inhalation resulted in higher NP uptake by alveolar epithelial cells in Cftr mutants. Instillation of carbon NP induced a comparable acute and transient inflammatory response in both genotypes. The twofold increase of bronchoalveolar lavage (BAL) neutrophils in Cftr mutant compared to wild type mice at day 3 but not at days 1 and 7, indicated an impaired capacity in inflammation resolution in Cftr mutants. Concomitant to the delayed decline of neutrophils, BAL granulocyte-colony stimulating factor was augmented in Cftr mutant mice. Anti-inflammatory 15-hydroxyeicosatetraenoic acid was generally significantly lower in BAL of Cftr mutant than in wild type mice. CONCLUSIONS: Despite lacking alterations in lung deposition and biokinetics of inhaled NP, and absence of significant differences in lung function, higher uptake of NP by alveolar epithelial cells and prolonged, acute inflammatory responses to NP exposure indicate a moderately increased susceptibility of lungs to adverse effects of inhaled NP in Cftr mutant mice and provides potential mechanisms for the increased susceptibility of CF patients to air pollution.
Asunto(s)
Contaminantes Atmosféricos/farmacocinética , Contaminantes Atmosféricos/toxicidad , Fibrosis Quística/patología , Nanopartículas/toxicidad , Contaminación del Aire , Animales , Líquido del Lavado Bronquioalveolar , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Modelos Animales de Enfermedad , Femenino , Inmunohistoquímica , Exposición por Inhalación , Iridio/farmacocinética , Iridio/toxicidad , Radioisótopos de Iridio , Pulmón/efectos de los fármacos , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos CFTR , Ratones Transgénicos , Microscopía Electrónica de Transmisión , Neumonía/inducido químicamente , Neumonía/patología , Pruebas de Función Respiratoria , Titanio/toxicidadRESUMEN
BACKGROUND: The six Platinum group metal elements (PGEs) comprising Ruthenium, Rhodium, Palladium, Platinum, Iridium and Osmium are grouped together in the periodic table. Human activities are mostly responsible for releasing PGEs into the environment. This systematic review focused on three PGEs with the greatest anthropogenic use, including in vehicle catalytic converters: Platinum (Pt), Palladium (Pd), and Rhodium (Rh). Consequently, these represent the greatest contributors to environmental pollution. The current review of in vivo toxicological studies (mammalian models) and in vitro cell exposure studies examined the potential harmful effects of these metalloids to mammalians, and their possible toxicity to human health. METHODS: We applied Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology to conduct a comprehensive search and evaluation of records in the available literature published between 01/01/2009 and 01/15/2024 in four databases. PROSPERO code ID: CRD42024471558. Results concerning the health effects of PGEs were extracted from articles according to the inclusion and exclusion criteria. After screening the records for eligibility, 22 studies were included in the final analysis. RESULTS: This systematic review revealed that airborne PGEs significantly increased the activation of pathologic pathways in several human organs and/or perturbed various metabolic pathways. In view of the known pro-inflammatory and organ-degenerative effects of PGEs, the paucity of studies on the effect of PGEs on the central nervous system and on possible correlations with neurodegenerative diseases were particularly evident. CONCLUSIONS: The clinical complexity and chronic nature of PGE-related pathologies indicate that targeted research is essential. In light of the increasing incidence of non-communicable diseases, particular attention should be paid to the design of epidemiological studies and to environmental monitoring services.
Asunto(s)
Platino (Metal) , Humanos , Animales , Platino (Metal)/toxicidad , Rodio/toxicidad , Iridio/toxicidad , Iridio/química , Paladio/toxicidad , Rutenio/químicaRESUMEN
Veterinary antibiotics have become an emerging pollutant in water and wastewater sources due to excess usage, toxicity and resistance to traditional water and wastewater treatment. The present study explored the degradation of a model antibiotic- Florfenicol (FF) using electrochemical oxidation (EO) with Ti-RuO2/IrO2 anode. The anode material was characterized using SEM-EDS studies expressing stable structure and optimal interaction of the neighboring metal oxides with each other. The EDS results showed the presence of Ru, Ir, Ti, O and C elements with 6.44%, 2.57%, 9.61%, 52.74% and 28.64% atomic weight percentages, respectively. Optimization studies revealed pH 5, 30 mA cm-2 current density and 0.05 M Na2SO4 for 5 mg L-1 FF achieved 90% TOC removal within 360 min treatment time. The degradation followed pseudo-first order kinetics. LC-Q-TOF-MS studies revealed six predominant byproducts illustrating hydroxylation, deflourination, and dechlorination to be the major degradation mechanisms during the electrochemical oxidation of FF. Ion chromatography studies revealed an increase in Cl-, F- and NO3- ions as treatment time progressed with Cl- decreasing after the initial phase of the treatment. Toxicity studies using Zebrafish (Danio rerio) embryo showed the treated sample to be toxic inducing developmental disorders such as pericardial edema, yolk sac edema, spinal curvature and tail malformation at 96 h post fertilization (hpf). Compared to control, delayed hatching and coagulation were observed in treated embryos. Overall, this study sets the stage for understanding the effect of mixed metal oxide (MMO) anodes on the degradation of veterinary antibiotic-polluted water and wastewater sources using electrochemical oxidation.
Asunto(s)
Antibacterianos , Electrodos , Oxidación-Reducción , Óxidos , Tianfenicol , Contaminantes Químicos del Agua , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/toxicidad , Tianfenicol/análogos & derivados , Tianfenicol/química , Tianfenicol/toxicidad , Óxidos/química , Óxidos/toxicidad , Animales , Antibacterianos/química , Antibacterianos/toxicidad , Aguas Residuales/química , Técnicas Electroquímicas , Iridio/química , Iridio/toxicidad , Cinética , Titanio/química , Titanio/toxicidad , Metales/química , Metales/toxicidad , Compuestos de RutenioRESUMEN
Despite the widespread use of iridium (Ir) in catalytic converters for improved capacity for reducing carbon monoxide (CO), hydrocarbon (HC) and nitrogen oxide (NO(x)) emissions, there is a lack of studies that have assessed possible toxicological hazards of exposure to Ir. The present investigation indicates that female Wistar rats exposed to Ir in the drinking water for 90 days displayed renal toxicity based on the elevated urinary retinol binding protein (RBP) and albumin. The RBP was more sensitive to albumin, showing significant increases at 0.01 mg/L.
Asunto(s)
Iridio/toxicidad , Enfermedades Renales/inducido químicamente , Riñón/fisiopatología , Albuminuria/inducido químicamente , Animales , Agua Potable , Contaminantes Ambientales/toxicidad , Femenino , Iridio/orina , Ratas , Ratas Wistar , Proteínas de Unión al Retinol/orina , Pruebas de Toxicidad Subcrónica , Microglobulina beta-2/orinaRESUMEN
Carbene-based macromolecules are an emerging new stimuli-sensitive class of biomaterials that avoid the impediments of free radical polymerization but maintain a rapid liquid-to-biorubber transition. Activation of diazirine-grafted polycaprolactone polyol (CaproGlu) is limited to UVA wavelengths that have tissue exposure constraints and limited light intensities. For the first time, UVA is circumvented with visible light-emitting diodes at 445 nm (blue) to rapidly activate diazirine-to-carbene covalent cross-linking. Iridium photocatalysts serve to initiate diazirine, despite having little to no absorption at 445 nm. CaproGlu's liquid organic matrix dissolves the photocatalyst with no solvents required, creating a light transparent matrix. Considerable differences in cross-linking chemistry are observed in UVA vs visible/photocatalyst formulations. Empirical analysis and theoretical calculations reveal a more efficient conversion of diazirine directly to carbene with no diazoalkane intermediate detected. Photorheometry results demonstrate a correlation between shear moduli, joules light dose, and the lower limits of photocatalyst concentration required for the liquid-to-biorubber transition. Adhesion strength on ex vivo hydrated tissues exceeds that of cyanoacrylates, with a fixation strength of up to 20 kg·f·cm2. Preliminary toxicity assessment on leachates and materials directly in contact with mammalian fibroblast cells displays no signs of fibroblast cytotoxicity.
Asunto(s)
Adhesivos/química , Materiales Biocompatibles/química , Complejos de Coordinación/química , Diazometano/análogos & derivados , Animales , Catálisis/efectos de la radiación , Colágeno/química , Complejos de Coordinación/efectos de la radiación , Complejos de Coordinación/toxicidad , Reactivos de Enlaces Cruzados/química , Iridio/química , Iridio/efectos de la radiación , Iridio/toxicidad , Luz , Ratones , Células 3T3 NIH , Poliésteres/química , PorcinosRESUMEN
Due to conventional photodynamic therapy encountering serious problems of phototoxicity and low tissue-penetrating depth of light, other dynamic therapy-based therapeutic methods such as sonodynamic therapy (SDT) are expected to be developed. To improve the therapeutic response to SDT, more effective sonosensitizers are imperative. In this study, a novel water-soluble iridium(III)-porphyrin sonosensitizer (IrTMPPS) was synthesized and used for SDT. IrTMPPS generated ample singlet oxygen (1O2) under US irradiation and especially showed distinguished US-activatable abilities at more than 10 cm deep-tissue depths. Interestingly, under US irradiation, IrTMPPS sonocatalytically oxidized intracellular NADH, which would enhance SDT efficiency by breaking the redox balance in the tumor. Moreover, IrTMPPS displayed great sonocytotoxicity toward various cancer cells, and in vivo experiments demonstrated efficient tumor inhibition and anti-metastasis to the lungs in the presence of IrTMPPS and US irradiation. This report gives a novel idea of metal-based sonosensitizers for sonotherapy by fully taking advantage of non-invasiveness, water solubility, and deep tumor therapy.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Porfirinas/uso terapéutico , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Animales , Antineoplásicos/síntesis química , Antineoplásicos/toxicidad , Línea Celular Tumoral , Iridio/química , Iridio/uso terapéutico , Iridio/toxicidad , Ratones , NAD/química , NAD/metabolismo , Neoplasias/patología , Oxidación-Reducción , Porfirinas/síntesis química , Porfirinas/toxicidad , Fármacos Sensibilizantes a Radiaciones/síntesis química , Fármacos Sensibilizantes a Radiaciones/toxicidad , Oxígeno Singlete/metabolismo , Ondas Ultrasónicas , Pez CebraRESUMEN
We report the synthesis, characterization, and photophysical properties of a new class of luminescent cyclometalated iridium(III) polypyridine poly(ethylene glycol) (PEG) complexes [Ir(N--C)(2)(N--N)](PF(6)) (HN--C=Hppy (2-phenylpyridine), N--N=bpy-CONH-PEG1 (bpy=2,2'-bipyridine; 1a), bpy-CONH-PEG3 (1b); HN--C=Hpq (2-phenylquinoline), N--N=bpy-CONH-PEG1 (2a), bpy-CONH-PEG3 (2b); HN--C=Hpba (4-(2-pyridyl)benzaldehyde), N--N=bpy-CONH-PEG1 (3)) and their PEG-free counterparts (N--N=bpy-CONH-Et, HN--C=Hppy (1c); HN--C=Hpq (2c)). The cytotoxicity and cellular uptake of these complexes have been investigated by the MTT assay, ICPMS, laser-scanning confocal microscopy, and flow cytometry. The results showed that the complexes supported by the water-soluble PEG can act as biological probes and labels with considerably reduced cytotoxicity. Because the aldehyde groups of complex 3 are reactive toward primary amines, the complex has been utilized as the first luminescent PEGylation reagent. Bovine serum albumin (BSA) and poly(ethyleneimine) (PEI) have been PEGylated with this complex, and the resulting conjugates have been isolated, purified, and their photophysical properties studied. The DNA-binding and gene-delivery properties of the luminescent PEI conjugate 3-PEI have also been investigated.
Asunto(s)
Iridio/química , Compuestos Organometálicos/síntesis química , Polietilenglicoles/química , Polímeros/química , Albúmina Sérica Bovina/química , Animales , Bovinos , Electroquímica , Iridio/toxicidad , Luminiscencia , Estructura Molecular , Compuestos Organometálicos/química , Compuestos Organometálicos/toxicidad , Polietilenglicoles/toxicidad , Unión Proteica , Albúmina Sérica Bovina/metabolismoRESUMEN
Currently, translocation of inhaled insoluble nanoparticles (NP) across membranes like the air-blood barrier into secondary target organs (STOs) is debated. Of key interest are the involved biological mechanisms and NP parameters that determine the efficiency of translocation. We performed NP inhalation studies with rats to derive quantitative biodistribution data on the translocation of NP from lungs to blood circulation and STOs. The inhaled NP were chain aggregates (and agglomerates) of either iridium or carbon, with primary particle sizes of 2-4 nm (Ir) and 5-10 nm (C) and aggregate sizes (mean mobility diameters) between 20 and 80 nm. The carbon aggregates contained a small fraction ( < 1%) of Ir primary particles. The insoluble aggregates were radiolabeled with (192)Ir. During 1 h of inhalation, rats were intubated and ventilated to avoid extrathoracic NP deposition and to optimize deep lung NP deposition. After 24 h, (192)Ir fractions in the range between 0.001 and 0.01 were found in liver, spleen, kidneys, heart, and brain, and an even higher fraction (between 0.01 and 0.05) in the remaining carcass consisting of soft tissue and bone. The fractions of (192)Ir carried with the carbon NP retained in STOs, the skeleton, and soft tissue were significantly lower than with NP made from pure Ir. Furthermore, there was significantly less translocation and accumulation with 80-nm than with 20-nm NP aggregates of Ir. These studies show that both NP characteristics--the material and the size of the chain-type aggregates--determine translocation and accumulation in STOs, skeleton, and soft tissue.
Asunto(s)
Barrera Alveolocapilar/metabolismo , Carbono/farmacocinética , Exposición por Inhalación , Iridio/farmacocinética , Nanopartículas , Aerosoles , Animales , Carbono/sangre , Carbono/toxicidad , Intubación Intratraqueal , Iridio/sangre , Iridio/toxicidad , Pulmón/metabolismo , Masculino , Nanopartículas/toxicidad , Tamaño de la Partícula , Permeabilidad , Ratas , Ratas Endogámicas WKY , Distribución TisularRESUMEN
Sodium hexachloroiridate injected 1 day after i.p. injection of 10(6) mouse ovarian tumor cells prevents the appearance of ascitic tumors in mice. Mice given injections of tumor cells all die at 20 to 30 days after tumor injection. Mice treated with sodium hexachloroiridate after tumor injection either have significant prolongation of life span without ascites or show no evidence of cancer even up to 7 months after tumor injection.
Asunto(s)
Iridio/toxicidad , Neoplasias Ováricas/patología , Animales , Cisplatino/uso terapéutico , Evaluación Preclínica de Medicamentos , Femenino , Inyecciones Intraperitoneales , Iridio/uso terapéutico , Ratones , Ratones Endogámicos C3H , Trasplante de Neoplasias , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/patología , Neoplasias Ováricas/tratamiento farmacológico , Distribución TisularRESUMEN
A new osmium-191 leads to iridium-191m generator suitable for first-pass radionuclide angiocardiography has been developed. This generator system allows repeated elutions of 4.96-sec iridium-191m from its 15.4-day Os- 191 parent. The Os-191 is loaded on an anion-exchange column (AGMP-1) and Ir- 191m eluted with 0.9% NaCl at pH 1. Each elution (0.6 to 1 ml) of the generator yields about 7 to 10% Ir-191m and gives 0.003-0.008% of Os-191 breakthrough. Toxicity studies of the generator eluate carried out in animals support the safety of using iridium-191m in humans. The long shelf-life of the generator (approximately equal to 2 wk) will allow medical centers to use Ir- 191m for routine clinical diagnosis. Iridium-191m obtained by this method should find additional useful applications in nuclear medicine.
Asunto(s)
Iridio , Osmio , Radioisótopos , Generadores de Radionúclidos , Animales , Carga Corporal (Radioterapia) , Fenómenos Químicos , Química , Vasos Coronarios/diagnóstico por imagen , Perros , Corazón/diagnóstico por imagen , Humanos , Lactante , Recién Nacido , Iridio/toxicidad , Ratones , Conejos , Cintigrafía , Factores de Tiempo , Distribución TisularRESUMEN
A group of 4 organometallic complexes of Rhodium (I) and 1 Iridium(I) was tested for the evaluation of their anti-inflammatory activity on carrageenin paw edema in rats. All the compounds used inhibited the development of paw edema by more than 50% at different dose-levels. The activity of the pyridinalmethylimine derivative [Rh(COD)PMI]+ Cl- had better results than that of [Rh(NBD)PMI]+ Cl- and even more than the dimeric complexes tested. The higher activity of [Ir(COD)Cl]2 as compared with [Rh(COD)Cl]2 suggests that it would be of interest to examine further Iridium(I) complexes, among which [Ir(COD)PMI]+ Cl- could be a good candidate.
Asunto(s)
Edema/prevención & control , Iridio/uso terapéutico , Compuestos Organometálicos/uso terapéutico , Rubidio/uso terapéutico , Animales , Carragenina , Edema/inducido químicamente , Iridio/toxicidad , Masculino , Compuestos Organometálicos/toxicidad , Ratas , Ratas Endogámicas , Rubidio/toxicidadRESUMEN
A health risk assessment of platinum (Pt) emitted from automotive catalytic converters is presented. Following a stepwise approach, the relevant literature is discussed in order to characterize Pt emissions as well as the toxic potential of Pt and its compounds. In an exposure assessment, ambient Pt concentrations in air are predicted to range from approximately 4 pg/m3 (street canyon, typical conditions) up to approximately 112 pg/m3 (express motorway, severe conditions). These values agree well with the few measured concentrations, which are also in the low pg/m3 range. Pt is emitted from catalytic converters in very small amounts (ng/km range), mainly in the (0)-oxidation state (elemental Pt). The nanocrystalline Pt particles are attached to microm-sized aluminum oxide particles. Whether free ultrafine Pt particles may be emitted and result in biological effects has not been studied sufficiently. Hence, risk assessment can only be based on the respiratory sensitizing potential of halogenated Pt salts. The presence of such compounds in automotive Pt emissions cannot definitely be excluded. From recent occupational studies conducted in catalytic converter production, a conservative no-effect level (NOEL) of 1.5 ng/m3 can be derived for the sensitizing effect of halogenated Pt salts. In a (reasonable) worst case approach, it is assumed that such compounds comprise 1% (0.1%) of the total Pt emissions. Applying a safety factor of 10 to account for interindividual variability, a guidance value of 15 (150) ng/m3 is derived for catalyst-borne Pt. The exposure to Pt in ambient air as measured or predicted is at least two orders of magnitude below this guidance range. Rhodium is also contained in automotive catalysts, palladium has increasingly substituted Pt, and iridium-based catalysts have recently been introduced. Although the database on these platinum group metals is rather small, there is no evidence that they pose a health risk to the general population.
Asunto(s)
Metales Pesados/toxicidad , Medición de Riesgo , Emisiones de Vehículos/efectos adversos , Relación Dosis-Respuesta a Droga , Indicadores de Salud , Humanos , Iridio/análisis , Iridio/toxicidad , Paladio/análisis , Paladio/toxicidad , Tamaño de la Partícula , Platino (Metal)/análisis , Platino (Metal)/toxicidad , Compuestos de Platino/toxicidad , Rodio/análisis , Rodio/toxicidad , Emisiones de Vehículos/análisisRESUMEN
Europium(III)-based material showing special milliseconds photoluminescence lifetime has been considered as an ideal time-gated luminescence probe for bioimaging, but is still limited in application in luminescent small-animal bioimaging in vivo. Here, a water-soluble, stable, highly-luminescent nanosystem, Ir-Eu-MSN (MSN = mesoporous silica nanoparticles, Ir-Eu = [Ir(dfppy)2(pic-OH)]3Eu·2H2O, dfppy = 2-(2,4-difluorophenyl)pyridine, pic-OH = 3-hydroxy-2-carboxypyridine), was developed by an in situ coordination reaction to form an insoluble dinuclear iridium(III) complex-sensitized-europium(III) emissive complex within mesoporous silica nanoparticles (MSNs) which had high loading efficiency. Compared with the usual approach of physical adsorption, this in-situ reaction strategy provided 20-fold the loading efficiency (43.2%) of the insoluble Ir-Eu complex in MSNs. These nanoparticles in solid state showed bright red luminescence with high quantum yield of 55.2%, and the excitation window extended up to 470 nm. These Ir-Eu-MSN nanoparticles were used for luminescence imaging in living cells under excitation at 458 nm with confocal microscopy, which was confirmed by flow cytometry. Furthermore, the Ir-Eu-MSN nanoparticles were successfully applied into high-contrast luminescent lymphatic imaging in vivo under low power density excitation of 5 mW cm(-2). This synthetic method provides a universal strategy of combining hydrophobic complexes with hydrophilic MSNs for in vivo bioimaging.
Asunto(s)
Complejos de Coordinación , Europio , Iridio , Sustancias Luminiscentes , Nanopartículas , Dióxido de Silicio , Animales , Complejos de Coordinación/química , Complejos de Coordinación/toxicidad , Europio/química , Europio/toxicidad , Células HeLa , Humanos , Iridio/química , Iridio/toxicidad , Luz , Sustancias Luminiscentes/química , Sustancias Luminiscentes/toxicidad , Mediciones Luminiscentes , Ratones , Ratones Desnudos , Nanopartículas/química , Nanopartículas/toxicidad , Dióxido de Silicio/química , Dióxido de Silicio/toxicidad , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
Bright and stable CuInS2/ZnS@SiO2 nanoparticles with near-infrared (NIR) emission were competently prepared by incorporating the as-prepared hydrophobic CuInS2/ZnS quantum dots (QDs) directly into lipophilic silane micelles and subsequently an exterior silica shell was formed. The obtained CuInS2/ZnS@SiO2 nanoparticles homogeneously comprised both single-core and multicore remarkable CuInS2/ZnS QDs, while the silica shell thickness could be controlled to within 5-10 nm and their overall size was 17-25 nm. Also, the functionalized CuInS2/ZnS QDs encapsulated in the silica spheres, expedited their bioconjugation with holo-Transferrin (Tf) for further cancer cell imaging. The CuInS2/ZnS@SiO2 nanoparticles not only showed a dominant NIR band-edge luminescence at 650-720 nm with a quantum yield (QY) between 30 and 50%, without a recognized photoluminescence (PL) red shift, but also exhibited excellent PL and colloidal stability in aqueous media. Impressively, the cytotoxicity studies revealed minor suppression on cell viability under both CuInS2/ZnS@SiO2 and CuInS2/ZnS@SiO2@Tf concentrations up to 1 mg/mL. The application in live-cell imaging revealed that the potential of CuInS2/ZnS QDs as biocompatible, robust, cadmium-free, and brilliant NIR emitters is considered promising for fluorescent labels.
Asunto(s)
Materiales Biocompatibles , Cobre , Iridio , Luminiscencia , Neoplasias/diagnóstico , Puntos Cuánticos , Dióxido de Silicio/química , Espectroscopía Infrarroja Corta , Sulfuros , Compuestos de Zinc , Cobre/toxicidad , Diagnóstico por Imagen , Células HeLa , Humanos , Hidrodinámica , Interacciones Hidrofóbicas e Hidrofílicas , Iridio/toxicidad , Micelas , Nanopartículas/ultraestructura , Puntos Cuánticos/química , Puntos Cuánticos/toxicidad , Puntos Cuánticos/ultraestructura , Sulfuros/toxicidad , Ultrasonido , Compuestos de Zinc/toxicidadRESUMEN
Environmental concentration of the platinum group elements is increased in the last years due to their use in automobile catalytic converters. Limited data are available on the effects of such elements at a cellular level and on their toxicity, especially for rhodium and iridium which have been more recently introduced in use. The toxic effects of rhodium and iridium salts were analyzed on a normal diploid rat fibroblast cell line in vitro. Both salts halted cell growth in a dose- and time-dependent fashion by inhibiting cell cycle progression, inducing apoptosis and modulating the expression of cell cycle regulatory proteins. In fact, they both caused an accumulation of cells in the G2/M phase of the cell cycle and affected the expression levels of pRb, cyclins D1 and E, p21(Waf1) and p27(Kip1). DNA strand breaks, as assessed by comet test, and an increase in the intracellular levels of reactive oxygen species also occurred in exposed cell cultures. These findings suggest a potential toxicity of both iridium and rhodium salts and emphasize the need for further studies to understand their effects at a cellular level to enable a better assessment of their toxic effects and to identify ways for their modulation and/or prevention.
Asunto(s)
Proliferación Celular/efectos de los fármacos , Daño del ADN , Fibroblastos/efectos de los fármacos , Iridio/toxicidad , Rodio/toxicidad , Animales , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Proteínas de Ciclo Celular/metabolismo , Línea Celular , Supervivencia Celular/efectos de los fármacos , Ensayo Cometa , Fibroblastos/metabolismo , RatasRESUMEN
Cuprimine® and Syprine® are therapeutics approved by the USFDA to treat copper overload in Wilson Disease (a genetic defect in copper transport) by chelation and accelerated excretion of internally-deposited copper. These oral therapeutics are based on the respective active ingredients D-penicillamine (DPA) and N,N'-bis (2-aminoethyl) -1,2-ethanediamine dihydrochloride (Trien). Cuprimine is considered the primary treatment, although physicians are increasingly turning to Syprine as a first-line therapy. Both drugs exhibit oral systemic activity and low toxicity; their biological effects and safety are established. Previous in vivo studies using a rodent animal model established the decorporation potential of Cuprimine and Syprine for (60)Co and (210)Po. Currently these studies are being expanded to evaluate the in vivo decorporation efficacy of these drugs for several additional radionuclides. In this report, results of this investigation are discussed using the radionuclides (137)Cs, (60)Co, (192)Ir and (85)Sr. Short-term 48-h pilot studies were undertaken to evaluate DPA and Trien for their in vivo decorporation potential using male Wistar-Han rats. In these studies, a radionuclide solution was administered to the animals by intravenous (IV) injection, followed by a single IV dose of either DPA or Trien. Control animals received the radionuclide alone. Results show effective decorporation of (60)Co by DPA within the time frame evaluated. DPA and Trien were also modestly effective in decorporation of (137)Cs and (85)Sr, respectively. The study did not find DPA or Trien effective for decorporation of (192)Ir. Based on these encouraging findings, further studies to evaluate the dose-response profiles and timing of the chelator administration post exposure to radionuclides are warranted.
Asunto(s)
Monitoreo de Radiación/métodos , Radioisótopos/toxicidad , Animales , Cesio/administración & dosificación , Cesio/farmacocinética , Cesio/toxicidad , Cobalto/administración & dosificación , Cobalto/farmacocinética , Cobalto/toxicidad , Inyecciones Intraventriculares , Iridio/administración & dosificación , Iridio/farmacocinética , Iridio/toxicidad , Masculino , Proyectos Piloto , Radioisótopos/administración & dosificación , Radioisótopos/farmacocinética , Ratas , Ratas Wistar , Medición de Riesgo/métodos , Estroncio/administración & dosificación , Estroncio/farmacocinética , Estroncio/toxicidad , Distribución TisularRESUMEN
When measuring the dielectric properties of aqueous samples, the impedance of the electrode/sample interface can limit low frequency measurements. The electrode polarization problem can be reduced by increasing the effective surface area of the electrodes. In this work, impedance spectroscopy was used to characterize and compare three different electrode surfaces that can be used to mitigate this effect: platinum black, iridium oxide, and [polypyrrole/poly(styrenesulphonate)] (PPy/PSS) conducting polymer. All three materials were directly compared with a bright platinum electrode. Equivalent circuit models were used to extract the increase in the effective surface area of the electrodes: platinum black, iridium oxide and PPy/PSS increase the effective capacitance of the electrode by factors of approximately 240, 75, and 790, respectively. The practical aspects of all electrode materials are discussed. These results suggest that iridium oxide and PPy/PSS are good alternatives to the commonly used platinum black, which is prone to mechanical damage (scratches) and is potentially toxic to cells.