Layered terbium hydroxides for simultaneous drug delivery and imaging.

Layered rare-earth hydroxides have begun to gather increasing attention as potential theranostic platforms owing to their extensive intercalation chemistry combined with magnetic and fluorescent properties. In this work, the potential of layered terbium hydroxide (LTbH) as a platform for simultaneous drug delivery and fluorescence imaging was evaluated. LTbH-Cl ([Tb2(OH)5]Cl·yH2O) was loaded with three nonsteroidal anti-inflammatory drugs (diclofenac, ibuprofen, and naproxen) via ion-exchange. Drug release studies in phosphate buffered saline (pH = 7.4) revealed all three formulations release their drug cargo rapidly over the course of approximately 5 hours. In addition, solid state fluorescence studies indicated that fluorescence intensity is strongly dependent on the identity of the guest anion. It was postulated that this feature may be used to track the extent of drug release from the formulation, which was subsequently successfully demonstrated for the ibuprofen loaded LTbH. Overall, LTbH exhibits good biocompatibility, high drug loading, and a strong, guest-dependent fluorescence signal, all of which are desirable qualities for theranostic applications.

Intensity Enhanced Cerenkov Luminescence Imaging Using Terbium-Doped Gd2O2S Microparticles.

Weak intensity and poor penetration depth are two big obstacles toward clinical use of Cerenkov luminescence imaging (CLI). In this proof-of-concept study, we overcame these limitations by using lanthanides-based radioluminescent microparticles (RLMPs), called terbium doped Gd2O2S. The characterization experiment showed that the emission excited by Cerenkov luminescence can be neglected whereas the spectrum experiment demonstrated that the RLMPs can actually be excited by γ-rays. A series of in vitro experiments demonstrated that RLMPs significantly improve the intensity and the penetration capacity of CLI, which has been extended to as deep as 15 mm. In vivo pseudotumor study further prove the huge potential of this enhancement strategy for Cerenkov luminescence imaging in living animal studies.

MOF@activated carbon: a new material for adsorption of aldicarb in biological systems.

A new composite was synthesized by the hydrothermal method using a 3D coordination network [Ln2(C4H4O4)3(H2O)2]·H2O (Ln = Eu and Tb) and activated carbon. The coordination network is formed within the pores of the charcoal, allowing for the use of this material as a detoxifying agent.

Lysosomes of the liver and the duodenal enterocytes, a site of handling of two rare earths. Ultrastructural and microanalytical study.

The frequent use of some trace elements such as gadolinium and terbium in medicine and modern industries make us worry about their behavior in the organism. In this work, we study the intracellular localization in the liver and in the intestinal mucosa of two rare earths, gadolinium and terbium, after intraperitoneal and intragastric administration. Three methods of observation and microanalysis were used: conventional transmission electron microscopy, secondary ion mass spectrometry, and electron probe microanalysis. After intraperitoneal administration, gadolinium and terbium were detected with phosphorus in lysosomes of hepatocytes and Küppfer cells and in territories near to biliary canalicule. One hour after intragastric administration, gadolinium and terbium were concentrated in lysosomes of the apical part of duodenal enterocytes. No gadolinium or terbium was detected in duodenum 4 days after administration. After intragastric administration, the microanalytical techniques failed to detect gadolinium or terbium in liver whatever the time of sampling. This mechanism of concentration-precipitation in the lysosomes of enterocytes limits the diffusion through the digestive barrier of foreign elements and then permits their elimination with apoptotic cells in the intestinal lumen. Some of these elements may be toxic, and none of them have a recognized physiological function. The intestinal mucosa plays an important role in the protection of the organism against the invasion of foreign elements.

Human biokinetics of inhaled terbium oxide.

Four healthy men inhaled a monodisperse aerosol of 160Tb-labelled terbium oxide particles. The behaviour of the tracer was studied through measurements of body radioactivity and of its urinary and faecal excretion. Estimated early faecal losses in the four subjects ranged from 3% to 31% of the initial respiratory-tract deposit; most of the residue had become systemic within a year, with the principal deposit apparently in bone. Interference from this systemic deposit prevented accurate determination of the long-term pulmonary clearance kinetics, but the pattern was broadly what would be expected for Type M materials in the ICRP's Human Respiratory Tract Model. Averaged trends in the whole-body residue after approximately 1 year suggest a clearance half-life of approximately to 5 y.

Distribution of terbium and increase of calcium concentration in the organs of mice i.v.-administered with terbium chloride.

To investigate the biological effects of terbium (Tb), male mice were intravenously administered with TbCl3 at 10, 25, or 50 mg Tb/kg. Time-course and dose-related changes in organ distributions of Tb were determined. More than 95% of the Tb in blood was in plasma, and the concentrations decreased rapidly. Contrary to normal pharmacokinetics, Tb concentrations in plasma were higher in the 10 mg/kg group than in the 50 mg/kg group. The concentrations after injection of 25 mg/kg were between 10 and 50 mg/kg injections. Tb was incorporated mainly in liver, lung, and spleen. In all groups more than 80% of Tb administered were found in these three organs. Disappearance of Tb in these organs was very slow. Tb was also found in kidney, heart and other organs. Coincidentally, it was found that the Ca concentration was increased in organs in which Tb was incorporated. After administration of Tb (50 mg/kg) the Ca concentration, compared to the controls, was 70-fold in spleen, 20-fold in lung, and 6-fold in liver. There were highly positive correlations between Tb and Ca concentrations in organs. Excretion of Tb in urine was 0.15-0.3% and that in feces was 1.7-12.5% for up to 7 days. These results indicate that liver, lung, and spleen are the main target organs of Tb administered intravenously, and that the increase in Ca concentrations is one of the important biological effects of Tb in target organs.

Pulmonary toxicity of systemic terbium chloride in mice.

Terbium (Tb) is a rare earth metal that finds use in several emerging technologies. However, little is known about the biological effects of Tb. Thus, in this study the pulmonary toxicity of systemic Tb in mice was investigated. Mice were treated intravenously with a single dose of 20 or 200 mumol Tb/kg, as TbCly and killed at 3, 6, 12, 24, 48, or 72 h later. Administration of Tb at a dose of 200 mumol/kg increased pulmonary weight, lipid peroxidation, and protein content but decreased pulmonary glutathione content. Pulmonary gamma-glutamyl transpeptidase (gamma-GTP) activity was increased after Tb administration at a dose of 200 mumol/kg. Pulmonary alkaline phosphatase (ALP) activity was also increased after Tb administration at a dose of 200 mumol/kg. Investigation of the defense system against oxidative damage in the lung showed that superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were all decreased after Tb administration at the higher dose. The concentrations of Tb, Ca, and P in lung was increased by the dose of 200 mumol/kg. These results suggest that pulmonary lipid peroxidation may be an early and sensitive consequence of Tb exposure and that SOD, CAT, and GSH-Px might be considered as potential modulators of Tb-induced lipid peroxidation. The mechanisms involved in Tb-induced pulmonary lipid peroxidation deserve further study.

Effect of terbium on protease activity in pancreas of mice.

The effect of terbium (Tb) on the protease activity in pancreas of mice was studied. Administration of Tb at doses of 20 and 200 mumol/kg increased the activities of trypsin and carboxypeptidase A, but did not affect the activities of chymotrypsin and carboxypeptidase B. High Tb concentrations were found in the liver and spleen compared to the kidney and pancreas. Increases in Ca concentrations in the pancreas, kidney, and spleen after Tb administration were observed. The pancreatic slice experiments showed the increase in trypsin activity after Tb treatment and increases in trypsin and carboxypeptidase A after Ca treatment. Tb inhibited strongly the activities of authentic chymotrypsin and carboxypeptidase A. These results suggest that the increase in trypsin activity in the pancreas after Tb administration results from the activation of trypsinogen by Tb and Ca ions and that the increase in carboxypeptidase A activity is due to the activation of procarboxypeptidase A by trypsin and Ca ion, which increased after Tb administration.