Molybdenum Dioxide (MoS2)/Gadolinium (Gd) Containing Arginine-Glycine-Aspartic Acid (RGD) Sequences as New Nano-Contrast Agent for Cancer Magnetic Resonance Imaging (MRI)

2021 ◽  
Vol 21 (3) ◽  
pp. 1403-1412
Author(s):  
Xiaoguang Hao ◽  
Weijing Li
Keyword(s):  
Particle Size ◽  
Contrast Agent ◽  
Contrast Agents ◽  
Aspartic Acid ◽  
Nude Mice ◽  
Molybdenum Dioxide ◽  
Signal Value ◽  
Arginine Glycine Aspartic Acid

Molybdenum dioxide-gadolinium-arginine/glycine/aspartic acid (MoS2-Gd-RGD) sequences targeting nano-contrast agents that specifically bind to human hepatocellular carcinoma (HCC) HepG2 cells were synthesized, and their targeting imaging effects on HCC cells and models were evaluated. Zeta potential, particle size and Fourier Transform Infrared Spectrometer (FTIR) were used to characterize the nano-contrast agent, and its cytotoxicity was evaluated. The MoS2-Gd nanoparticles were used as control in vitro to determine the targeting capability of the MoS2-Gd-RGD nanoparticles toward integrin αvβ3. During in vivo animal experiments, 12 nude mice with tumors were randomly divided into three groups to compare the imaging effects of the MoS2-Gd-RGD and MoS2-Gd groups. The hydrodynamic diameter of MoS2-Gd-RGD nanoparticles was approximately 336.43±6.43 nm, and the polydispersity index (PDI) value reached 0.132. Transmission electron microscopy showed the uniform particle size and good dispersion of the nanoparticles. The relaxation rate totaled 1.39 mM−1S−1. The signal value of the T1-weighted image of the HepG2 cells treated with MoS2-Gd-RGD was higher than that of the non-targeted materials (MoS2-Gd) (P < 0.01). The signal value of the tumor increased significantly 15 min after the tail vein injection with MoS2-Gd-RGD, and it peaked at 60 min after injection. A significant difference in tumor signal values was observed between the two groups of nude mice injected with MoS2-Gd-RGD and MoS2- Gd (P < 0.01). At the in vitro and in vivo experiments, the MoS2-Gd-RGD nanoparticles presented the characteristics of integrin αvβ3 targeting. Thus, MoS2-Gd-RGD nanoparticles feature potential as contrast agents for MRI.

scholarly journals Study on Establishing Reference Safe Concentrations of MRI Contrast Agents for Optimized Images: Paramagnetic Gd-DTPA-BMEA and Superparamagnetic Ferucarbotran

2021 ◽  
Vol 11 (3) ◽  
pp. 1165
Author(s):  
Wen-Tien Hsiao ◽  
Yi-Hong Chou ◽  
Jhong-Wei Tu ◽  
Ai-Yih Wang ◽  
Lu-Han Lai
Keyword(s):  
Contrast Agent ◽  
Contrast Agents ◽  
Mri Contrast Agents ◽  
Mri Contrast Agent ◽  
In Vitro Experiments ◽  
Mri Contrast ◽  
In Vivo Experiments ◽  
Contrast Agent Injection

The purpose of this study is to establish the minimal injection doses of magnetic resonance imaging (MRI) contrast agents that can achieve optimized images while improving the safety of injectable MRI drugs. Gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) and ferucarbotran, commonly used in clinical practice, were selected and evaluated with in vitro and in vivo experiments. MRI was acquired using T1-weighted (T1W) and T2-weighted (T2W) sequences, and the results were quantitatively analyzed. For in vitro experiments, results showed that T1W and T2W images were optimal when Gd-DTPA-bisamide (2-oxoethyl) (Gd-DTPA-BMEA) and ferucarbotran were diluted to a volume percentage of 0.6% and 0.05%; all comparisons were significant differences in grayscale statistics using one-way analysis of variance (ANOVA). For in vivo experiments, the contrast agent with optimal concentration percentages determined from in vitro experiments were injected into mice with an injection volume of 100 μL, and the images of brain, heart, liver, and mesentery before and after injection were compared. The statistical results showed that the p values of both T1W and T2W were less than 0.001, which were statistically significant. Under safety considerations for MRI contrast agent injection, optimized MRI images could still be obtained after reducing the injection concentration, which can provide a reference for the safety concentrations of MRI contrast agent injection in the future.

scholarly journals PEG-modified gadolinium nanoparticles as contrast agents for in vivo micro-CT

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Charmainne Cruje ◽  
P. Joy Dunmore-Buyze ◽  
Eric Grolman ◽  
David W. Holdsworth ◽  
Elizabeth R. Gillies ◽  
...  
Keyword(s):  
Contrast Agent ◽  
Contrast Agents ◽  
Soft Tissues ◽  
Three Dimensional ◽  
Blood Pool ◽  
Micro Ct ◽  
Micro Computed Tomography ◽  
Poly Ethylene

AbstractVascular research is largely performed in rodents with the goal of developing treatments for human disease. Micro-computed tomography (micro-CT) provides non-destructive three-dimensional imaging that can be used to study the vasculature of rodents. However, to distinguish vasculature from other soft tissues, long-circulating contrast agents are required. In this study, we demonstrated that poly(ethylene glycol) (PEG)-coated gadolinium nanoparticles can be used as a vascular contrast agent in micro-CT. The coated particles could be lyophilized and then redispersed in an aqueous solution to achieve 100 mg/mL of gadolinium. After an intravenous injection of the contrast agent into mice, micro-CT scans showed blood pool contrast enhancements of at least 200 HU for 30 min. Imaging and quantitative analysis of gadolinium in tissues showed the presence of contrast agent in clearance organs including the liver and spleen and very low amounts in other organs. In vitro cell culture experiments, subcutaneous injections, and analysis of mouse body weight suggested that the agents exhibited low toxicity. Histological analysis of tissues 5 days after injection of the contrast agent showed cytotoxicity in the spleen, but no abnormalities were observed in the liver, lungs, kidneys, and bladder.

scholarly journals A Spectral De-mixing Model for Triplex In Vivo Imaging of Optical Coherence Tomography Contrast Agents

2019 ◽  
Author(s):  
Edwin Yuan ◽  
Peng Si ◽  
Saba Shevidi ◽  
Adam de la Zerda
Keyword(s):  
Optical Coherence Tomography ◽  
Contrast Agent ◽  
Contrast Agents ◽  
In Vivo Imaging ◽  
Spectroscopic Technique ◽  
Optical Coherence ◽  
Single Voxel ◽  
Gold Nanobipyramids

The ability to detect multiple contrast agents simultaneously would greatly enhance Optical Coherence Tomography (OCT) images, providing nuanced biological context to physiological structures. However, previous OCT contrast agent work has been limited to scenarios where only a single contrast agent could be robustly detected within each voxel. We present a novel spectroscopic technique for de-mixing the spectral signal from multiple OCT contrast agents within a single voxel. We validate our technique in vitro and also demonstrate in vivo imaging of three spectrally distinct gold nanobipyramids, trafficking within the lymphatic system of a live mouse. This approach opens the door to a much broader range of pre-clinical and clinical OCT applications where multiplexed labeling is desirable.

Cyclic arginine-glycine-aspartic acid peptide inhibits macrophage infiltration of the kidney and carotid artery lesions in apo-E-deficient mice

2006 ◽  
Vol 290 (1) ◽  
pp. F159-F166 ◽  
Author(s):  
Saban Elitok ◽  
Sergey V. Brodsky ◽  
Daniel Patschan ◽  
Tatyana Orlova ◽  
Kenneth M. Lerea ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Aspartic Acid ◽  
Lipid Accumulation ◽  
Macrophage Infiltration ◽  
Artery Ligation ◽  
Apo E ◽  
Arginine Glycine Aspartic Acid ◽  
Deficient Mice

Interactions of leukocytes with the vascular endothelium culminating in their diapedesis represent not only a crucial event in immune surveillance and defense but are also critically involved in the pathogenesis of many inflammatory diseases, including atherosclerosis. Our previous in vitro studies using atomic force microscopy measurement of monocyte-endothelial cell interaction have demonstrated that a cyclic arginine-glycine-aspartic acid peptide (cRGD) inhibited their adhesion through very late antigen (α4β1-integrin; VLA4)-vascular cell adhesion molecule-1 by 60% with the IC50= 100 nM. To elucidate the potential efficacy of this peptide in vivo in preventing atherogenesis, experiments were performed in apolipoprotein E (ApoE)-deficient (−/−) mice fed a Western diet and receiving chronic treatment with cRGD peptide for 2–4 wk. In addition, some animals were subjected to a temporary carotid artery ligation while receiving the above treatment. Formation of fatty streaks and infiltration of the vascular wall with macrophages were not affected by cRGD treatment. Infiltration of the carotid artery postligation was significantly reduced in the cRGD-treated animals, as was the lipid accumulation. Furthermore, cRGD-treated ApoE−/−mice exhibited significantly lesser macrophage infiltration and lipid accumulation in the kidneys, the site of the highest expression of VLA4. These data demonstrated that cRGD peptide is a potent inhibitor of monocyte/macrophage infiltration of the injured macrovasculature and of the renal microvasculature, where it results in the attenuation of lipid accumulation. Formation of fatty streaks in the aortic root was not inhibitable by this treatment.

In Vitro and in Vivo Comparison of Binding of 99m-Tc-Iabeled Anti-CEA MAb F33-104 with 99m-Tc-labeled Anti-CEA MAb BW431/26

1999 ◽  
Vol 38 (04) ◽  
pp. 115-119
Author(s):  
N. Oriuchi ◽  
S. Sugiyama ◽  
M. Kuroki ◽  
Y. Matsuoka ◽  
S. Tanada ◽  
...  
Keyword(s):  
Nude Mice ◽  
Binding Capacity ◽  
Colon Adenocarcinoma ◽  
Human Colon ◽  
Cell Binding ◽  
Vitro Binding ◽  
Labeling Method ◽  
Human Colon Adenocarcinoma

Summary Aim: The purpose of this study was to assess the potential for radioimmunodetection (RAID) of murine anti-carcinoembryonic antigen (CEA) monoclonal antibody (MAb) F33-104 labeled with technetium-99m (99m-Tc) by a reduction-mediated labeling method. Methods: The binding capacity of 99m-Tc-labeled anti-CEA MAb F33-104 with CEA by means of in vitro procedures such as immunoradiometric assay and cell binding assay and the biodistribution of 99m-Tc-labeled anti-CEA MAb F33-104 in normal nude mice and nude mice bearing human colon adenocarcinoma LS180 tumor were investigated and compared with 99m-Tc-labeled anti-CEA MAb BW431/26. Results: The in vitro binding rate of 99m-Tc-labeled anti-CEA MAb F33-104 with CEA in solution and attached to the cell membrane was significantly higher than 99m-Tclabeled anti-CEA MAb BW431/261 (31.4 ± 0.95% vs. 11.9 ± 0.55% at 100 ng/mL of soluble CEA, 83.5 ± 2.84% vs. 54.0 ± 2.54% at 107 of LS 180 cells). In vivo, accumulation of 99m-Tc-labeled anti-CEA MAb F33-104 was higher at 18 h postinjection than 99m-Tc-labeled anti-CEA MAb BW431/26 (20.1 ± 3.50% ID/g vs. 14.4 ± 3.30% ID/g). 99m-Tcactivity in the kidneys of nude mice bearing tumor was higher at 18 h postinjection than at 3 h (12.8 ± 2.10% ID/g vs. 8.01 ± 2.40% ID/g of 99m-Tc-labeled anti-CEA MAb F33-104, 10.7 ± 1.70% ID/g vs. 8.10 ± 1.75% ID/g of 99m-Tc-labeled anti-CEA MAb BW431/26). Conclusion: 99m-Tc-labeled anti-CEA MAb F33-104 is a potential novel agent for RAID of recurrent colorectal cancer.

Tantalum Oxide Nanoparticles as Versatile Contrast Agents for X-ray Computed Tomography

2020 ◽  
Author(s):  
Shatadru Chakravarty ◽  
Jeremy Hix ◽  
Kaitlyn Wieweora ◽  
Maximilian Volk ◽  
Elizabeth Kenyon ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Contrast Agents ◽  
Mesoporous Silica Nanoparticles ◽  
Sol Gel ◽  
Tantalum Oxide ◽  
High Signal ◽  
Drug Delivery Vehicles ◽  
X Ray Computed

Here we describe the synthesis, characterization and in vitro and in vivo performance of a series of tantalum oxide (TaOx) based nanoparticles (NPs) for computed tomography (CT). Five distinct versions of 9-12 nm diameter silane coated TaOx nanocrystals (NCs) were fabricated by a sol-gel method with varying degrees of hydrophilicity and with or without fluorescence, with the highest reported Ta content to date (78%). Highly hydrophilic NCs were left bare and were evaluated in vivo in mice for micro-CT of full body vasculature, where following intravenous injection, TaOx NCs demonstrate high CT contrast, circulation in blood for ~ 3 h, and eventual accumulation in RES organs; and following injection locally in the mammary gland, where the full ductal tree structure can be clearly delineated. Partially hydrophilic NCs were encapsulated within mesoporous silica nanoparticles (MSNPs; TaOx@MSNPs) and hydrophobic NCs were encapsulated within poly(lactic-co-glycolic acid) (PLGA; TaOx@PLGA) NPs, serving as potential CT-imagable drug delivery vehicles. Bolus intramuscular injections of TaOx@PLGA NPs and TaOx@MSNPs to mimic the accumulation of NPs at a tumor site produce high signal enhancement in mice. In vitro studies on bare NCs and formuated NPs demonstrate high cytocompatibility and low dissolution of TaOx. This work solidifies that TaOx-based NPs are versatile contrast agents for CT.

Formulation and Evaluation of Nanosuspension of Simvastatin

2015 ◽  
Vol 8 (2) ◽  
pp. 2858-2873
Author(s):  
Rupali L. Shid ◽  
Shashikant N. Dhole ◽  
Nilesh Kulkarni ◽  
Santosh L Shid
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Factorial Design ◽  
Dissolution Rate ◽  
In Vitro Dissolution ◽  
Total Drug ◽  
23 Factorial Design ◽  
Rate Of Dissolution

Poor water solubility and slow dissolution rate are issues for the majority of upcoming and existing biologically active compounds. Simvastatin is poorly water-soluble drug and its bioavailability is very low from its crystalline form. The purpose of this study wasto increase the solubility and dissolution rate of simvastatin by the  preparation of nanosuspension by emulsification solvent diffusion method at laboratory scale. Prepared nanosus-pension was evaluated for its particle size and in vitro dissolution study and characterized by zeta potential,differential scanning calorimetry (DSC) and X-Ray diffractometry (XRD), motic digital microscopy, entrapment efficiency, total drug content, saturated solubility study and in vivo study. A 23 factorial design was employed to study the effect of independent variables, amount of SLS (X1), amount of PVPK-30 (X2) and poloxamer-188 (X3) and dependent variables are total drug content and polydispersity Index. The obtained results showed that particle size (nm) and rate of dissolution has been improved when nanosuspension prepared with the higherconcentration of PVPK-30 with the higher concentration of PVP K-30 and Poloxamer-188 and lower concentration of SLS. The particle size and zeta potential of optimized formulation was found to be 258.3 nm and 23.43. The rate of dissolution of the optimized nanosuspension was enhanced (90% in 60min), relative to plain simvastatin  (21% in 60 min), mainly due to the formation of nanosized particles. These results indicate the suitability of 23 factorial  design for preparation of simvastatin loaded nano-suspension significantly improved in vitro dissolution rate and thus possibly enhance fast onset of therapeutic drug effect. In vivo study shows increase in bioavailability in nanosuspension formulation than the plain simvastatin drug.

scholarly journals Obesity Potentiates Esophageal Squamous Cell Carcinoma Growth and Invasion by AMPK-YAP Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Jia-Huang Liu ◽  
Qi-Fei Wu ◽  
Jun-Ke Fu ◽  
Xiang-Ming Che ◽  
Hai-Jun Li
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Nude Mice ◽  
Serum Glucose ◽  
Migration And Invasion ◽  
Endocrine Effect

Obesity could increase the risk of esophageal squamous cell carcinoma (ESCC) and affect its growth and progression, but the mechanical links are unclear. The objective of the study was to explore the impact of obesity on ESCC growth and progression utilizing in vivo trials and cell experiments in vitro. Diet-induced obese and lean nude mice were inoculated with TE-1 cells, then studied for 4 weeks. Serum glucose, insulin, leptin, and visfatin levels were assayed. Sera of nude mice were obtained and then utilized to culture TE-1. MTT, migration and invasion assays, RT-PCR, and Western blotting were used to analyze endocrine effect of obesity on cell proliferation, migration, invasion, and related genes expression of TE-1. Obese nude mice bore larger tumor xenografts than lean animals, and were hyperglycemic and hyperinsulinemic with an elevated level of leptin and visfatin in sera, and also were accompanied by a fatty liver. As for the subcutaneous tumor xenograft model, tumors were more aggressive in obese nude mice than lean animals. Tumor weight correlated positively with mouse body weight, liver weight of mice, serum glucose, HOMA-IR, leptin, and visfatin. Obesity prompted significant TE-1 cell proliferation, migration, and invasion by endocrine mechanisms and impacted target genes. The expression of AMPK and p-AMPK protein decreased significantly ( P < 0.05 ); MMP9, total YAP, p-YAP, and nonphosphorylated YAP protein increased significantly ( P < 0.05 ) in the cells cultured with conditioned media and xenograft tumor from the obese group; the mRNA expression of AMPK decreased significantly ( P < 0.05 ); YAP and MMP9 mRNA expression increased significantly ( P < 0.05 ) in the cells exposed to conditioned media from the obese group. In conclusion, the altered adipokine milieu and metabolites in the context of obesity may promote ESCC growth in vivo; affect proliferation, migration, and invasion of ESCC cells in vitro; and regulate MMP9 and AMPK-YAP signaling pathway through complex effects including the endocrine effect.

scholarly journals In vitro and in vivo Evaluation of Ibuprofen Nanosuspensions for Enhanced Oral Bioavailability

2021 ◽  
Author(s):  
Mohsen Hedaya ◽  
Farzana Bandarkar ◽  
Aly Nada
Keyword(s):  
Particle Size ◽  
Tween 80 ◽  
Aqueous Solubility ◽  
In Vitro Dissolution ◽  
In Vivo Evaluation ◽  
Poorly Soluble ◽  
Extent Of Absorption ◽  
Better Than

Introduction: The objectives were to prepare, characterize and in vivo evaluate different ibuprofen (IBU) nanosuspensions prepared by ultra-homogenization, after oral administration to rabbits. Methods: The nanosuspensions produced by ultra-homogenization were tested and compared with a marketed IBU suspension for particle size, in vitro dissolution and in vivo absorption. Five groups of rabbits received orally 25 mg/kg of IBU nanosuspension, nanoparticles, unhomogenized suspension, marketed product and untreated suspension. A sixth group received 5 mg/kg IBU intravenously. Serial blood samples were obtained after IBU administration. Results: The formulated nanosuspensions showed significant decrease in particle size. Polyvinyl Pyrrolidone K30 (PP) was found to improve IBU aqueous solubility much better than the other tested polymers. Addition of Tween 80 (TW), in equal amount as PP (IBU: PP:TW, 1:2:2 w/w) resulted in much smaller particle size and better dissolution rate. The Cmax achieved were 14.8±1.64, 11.1±1.37, 9.01±0.761, 7.03±1.38 and 3.23±1.03 μg/ml and the tmax were 36±8.2, 39±8.2, 100±17.3, 112±15 and 105±17 min for the nanosuspension, nanoparticle, unhomogenized suspension, marketed IBU suspension and untreated IBU suspension in water, respectively. Bioavailability of the different formulations relative to the marketed suspension were the highest for nanosuspension> unhomogenized suspension> nanoparticles> untreated IBU suspension. Conclusion: IBU/PP/TW nanosuspensions showed enhanced in vitro dissolution as well as faster rate and higher extent of absorption as indicated from the higher Cmax, shorter tmax and larger AUC. The in vivo data supported the in vitro results. Nanosuspensions prepared by ultra-high-pressure-homogenization technique can be used as a good formulation strategy to enhance the rate and extent of absorption of poorly soluble drugs.

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