succimer and ferric-ferrocyanide

Adipose-derived stem cells (ADSCs) exhibit tremendous potential for repair of ischemic diseases. However, studies on the fate, migration, differentiation, and body distribution of the labeled ADSCs are rarely reported. In this study, magnetic iron oxide nanoparticles were designed, synthesized, and coated with meso-2,3-dimercaptosuccinic acid (DMSA) to produce DMSA nanoparticles (DMSA-NPs). The properties, size distribution, and characterization of DMSA-NPs were evaluated. Green fluorescent protein expressing ADSCs (GFP-ADSCs) were obtained and labeled with DMSA-NPs. The viability, cytotoxicity and multi-differentiation capacity of labeled GFP-ADSCs were evaluated in vitro. Labeled and non-labeled GFP-ADSCs were injected into a mouse model of hindlimb ischemia, and 3T magnetic resonance imaging (MRI) was acquired. The synthesized DMSA-NPs efficiently labeled the GFP-ADSCs in vitro and in vivo without affecting cell viability, proliferation, cell cycle, and multi-differentiation capacity. The MRI showed hypointense spots in the labeled GFP-ADSCs that lasted up to 8 weeks. Prussian blue staining and immunofluorescence assay at 4 and 8 weeks indicated that the labeled GFP-ADSCs were in and around the ischemic sites and some differentiated into capillaries. This observation is identical to that seen for transplants of unlabeled cells. Labeled cells were also identified mainly in the liver and spleen, with significantly smaller amounts in the lungs, intestines, heart, and kidney. Developed DMSA-NPs were shown to exhibit a considerable potential for use as nanoprobes for MRI of stem cells, which will enhance our understanding of cell-based therapeutic strategies for ischemic diseases.

Topics: Adipose Tissue; Animals; Cell Death; Cell Differentiation; Cell Survival; Disease Models, Animal; Ferric Compounds; Ferrocyanides; Flow Cytometry; Fluorescent Antibody Technique; Green Fluorescent Proteins; Hindlimb; Hydrodynamics; Immunohistochemistry; Ischemia; Magnetic Resonance Imaging; Mice; Mice, Inbred C57BL; Multipotent Stem Cells; Nanoparticles; Particle Size; Staining and Labeling; Stem Cell Transplantation; Stem Cells; Succimer

To investigate the targeting activity of the peptide (named P1c) derived from connective tissue growth factor (CTGF) to αvβ3-rich tumor cells.. P1c was synthesized and conjugated with ultrasuperparamagnetic iron oxide particles (USPIOs) coated with meso-2,3-dimercaptosuccinic acid (DMSA). The specific binding activity of P1c-USPIOs to αvβ3 was verified by solid phase binding assay. The combination of P1c-USPIOs with a human primary liver cancer cell (Bel 7402) with αvβ3-positive expression and uptake of P1c-USPIOs by cells was investigated by Prussian blue staining, transmission electron microscopy (TEM), and magnetic resonance imaging (MRI). The targeting activity of the probe in vivo was also evaluated using a small-animal tumor model by MRI.. The cell uptake of P1c-USPIOs was observed in a dose-dependent manner, whereas no significant particle uptake was found in the plain USPIOs group. The differences on T2*-weighted imaging were also found by MRI and the signal intensity (SI) was statistically reduced after coculture of Bel 7402 cells with P1c-USPIOs at a concentration of 20-80 μg/mL compared with plain USPIOs (P < 0.05). The in vivo study showed that the signal reduction was distributed mainly in the periphery and some central areas of the tumor. The tumor-to-muscle CNR (contrast-to-noise ratio) at 12 hours after the administration of the P1c-USPIOs was statistically significantly different compared to those at 0 hour, 1 hour, or the plain USPIO group (P < 0.05).. The peptide P1c might be a good candidate as a targeting carrier for drugs or tracers.

Topics: Cell Line, Tumor; Coloring Agents; Disease Progression; Ferric Compounds; Ferrocyanides; Humans; Integrin alphaVbeta3; Liver Neoplasms; Magnetic Resonance Imaging; Microscopy, Electron, Transmission; Neoplasm Metastasis; Peptides; Succimer

Despite being banned as a pesticide, thallium still results in human and animal poisonings. Current recommended treatments include the use of the chemical Prussian Blue. Limitations in its availability may result in Prussian Blue not being obtainable in the thallium-poisoned patient. The chelator 2,3-Dimercaptosuccinic acid (DMSA) is currently FDA-approved for use in childhood lead poisoning and has been reported to be beneficial in treating other heavy metal poisonings. The objective of this study was to determine the efficacy of DMSA as a treatment for thallium poisoning by studying mortality and whole-brain concentrations in thallium poisoned rats.. Rats were gavaged with 30 mg/kg of thallium. After 24 hours they were randomized to DMSA (n = 20) 50 mg/kg twice daily for 5 days, Prussian Blue (n = 20) 50 mg/kg twice daily for 5 days, or control (n = 30). Animals were monitored twice daily for weight loss and mortality. Animals losing greater than 20% of their starting weight were euthanized and counted as a mortality. All surviving rats at 120 hours had their brains harvested and digested and underwent subsequent thallium analysis.. The rate of survival in DMSA-treated animals compared to control was 45% vs. 21%, p = 0.07. Mean whole-brain thallium concentrations between DMSA and control rats were 3.4 vs. 3.0 microg/g, p = 0.06. Prussian Blue-treated rats had significantly improved survival (70% vs. 21%, p < 0.01) and lower whole-brain thallium concentrations (1.6 vs. 3.0 microg/g, p < 0.01 tissue) compared to controls.. DMSA failed to reduce brain thallium concentrations in rats poisoned with thallium and had an indeterminate effect on mortality while Prussian Blue significantly reduces both brain thallium concentrations and mortality.

Topics: Acute Disease; Animals; Antidotes; Brain; Ferrocyanides; Male; Rats; Rats, Sprague-Dawley; Succimer; Survival Analysis; Thallium; Tissue Distribution