scholarly journals Potential of Gold Nanoparticles for Noninvasive Imaging and Therapy for Vascular Inflammation

Author(s):  
Hisanori Kosuge ◽  
Maki Nakamura ◽  
Ayako Oyane ◽  
Kazuko Tajiri ◽  
Nobuyuki Murakoshi ◽  
...  

Abstract Purpose Macrophages contribute to the progression of vascular inflammation, making them useful targets for imaging and treatment of vascular diseases. Gold nanoparticles (GNPs) are useful as computed tomography (CT) contrast agents and light absorbers in photothermal therapy. In this study, we aimed to assess the viability of macrophages incubated with GNPs after near-infrared (NIR) laser light exposure and to evaluate the utility of intravenously injected GNPs for in vivo imaging of vascular inflammation in mice using micro-CT. Procedures Mouse macrophage cells (RAW 264.7) were incubated with GNPs and assessed for GNP cellular uptake and cell viability before and after exposure to NIR laser light. For in vivo imaging, macrophage-rich atherosclerotic lesions were induced by carotid ligation in hyperlipidemic and diabetic FVB mice (n = 9). Abdominal aortic aneurysms (AAAs) were created by angiotensin II infusion in ApoE-deficient mice (n = 9). These mice were scanned with a micro-CT imaging system before and after the intravenous injection of GNPs. Results The CT attenuation values of macrophages incubated with GNPs were significantly higher than those of cells incubated without GNPs (p < 0.04). Macrophages incubated with and without GNPs showed similar viability. The viability of macrophages incubated with GNPs (100 μg/ml or 200 μg/ml) was decreased by high-intensity NIR laser exposure but not by low-intensity NIR laser exposure. In vivo CT images showed higher CT attenuation values in diseased carotid arteries than in non-diseased contralateral arteries, although the difference was not statistically significant. The CT attenuation values of the perivascular area in AAAs of mice injected with GNPs were significantly higher than those of mice without injection (p = 0.0001). Conclusions Macrophages with GNPs had reduced viability upon NIR laser exposure. GNPs intravenously injected into mice accumulated in sites of vascular inflammation, allowing detection of carotid atherosclerosis and AAAs in CT imaging. Thus, GNPs have potential as multifunctional biologically compatible particles for the detection and therapy of vascular inflammation.

2021 ◽  
Vol 2 (4) ◽  
pp. 196-207
Author(s):  
Emanuel Sporer ◽  
Christian B. M. Poulie ◽  
Sture Lindegren ◽  
Emma Aneheim ◽  
Holger Jensen ◽  
...  

Targeted α-therapy (TAT) can eradicate tumor metastases while limiting overall toxicity. One of the most promising α-particle emitters is astatine-211 (211At). However, 211At-carbon bonds are notoriously unstable in vivo and no chelators are available. This hampers its adoption in TAT. In this study, the stability of 211At on the surface of gold nanoparticles (AuNPs) was investigated. The employed AuNPs had sizes in the 25–50 nm range. Radiolabeling by non-specific surface-adsorption in >99% radiochemical yield was achieved by mixing 211At and AuNPs both before and after polyethylene glycol (PEG) coating. The resulting 211At-AuNPs were first challenged by harsh oxidation with sodium hypochlorite, removing roughly 50% of the attached 211At. Second, incubation in mouse serum followed by a customized stability test, showed a stability of >95% after 4 h in serum. This high stability was further confirmed in an in vivo study, with comparison to a control group of free 211At. The AuNP-associated 211At showed low uptake in stomach and thyroid, which are hallmark organs of uptake of free 211At, combined with long circulation and high liver and spleen uptake, consistent with nanoparticle biodistribution. These results support that gold surface-adsorbed 211At has high biological stability and is a potentially useful delivery system in TAT.


2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e20557-e20557
Author(s):  
Tao Li ◽  
Chuan Yang ◽  
Guojun Zhang ◽  
Jianming Huang ◽  
Jiahua Lv ◽  
...  

2021 ◽  
Author(s):  
Rossana Terracciano ◽  
Aobo Zang ◽  
E. Brian Butler ◽  
Danilo Demarchi ◽  
Jason Hafner ◽  
...  

2022 ◽  
Author(s):  
Martina Mambrini ◽  
Laura Mecozzi ◽  
Erica Ferrini ◽  
Ludovica Leo ◽  
Davide Bernardi ◽  
...  

Abstract Micro-Computed Tomography (CT) imaging provides densitometric and functional assessment of lung diseases in animal models, playing a key role either in understanding disease progression or in drug discovery studies.The generation of reliable and reproducible experimental data is strictly dependent on a system’s stability. Quality Controls (QC) are essential to monitor micro-CT performance but, although QC procedures are standardized and routinely employed in clinical practice, detailed guidelines for preclinical imaging are lacking. In this work, we propose a routine QC protocol for in vivo micro-CT, based on three commercial phantoms. To investigate the impact of a detected scanner drift on image post-processing, a retrospective analysis using twenty-two healthy mice was performed and lung density histograms used to compare the Area Under Curve (AUC), the skewness and the kurtosis before and after the drift. As expected, statistically significant differences were found for all the selected parameters [AUC: 532 ± 31 vs. 420 ± 38 (p < 0.001); skewness: 2.3 ± 0.1 vs. 2.5 ± 0.1 (p < 0.001) and kurtosis: 4.2 ± 0.3 vs. 5.1 ± 0.5 (p < 0.001)], confirming the importance of the designed QC procedure to obtain a reliable longitudinal quantification of disease progression and drug efficacy evaluation.


2008 ◽  
Author(s):  
Russell Kincaid ◽  
Andrzej Krol ◽  
Sylvain Fourmaux ◽  
Jean-Claude Kieffer ◽  
Cristina Serbanescu ◽  
...  

2008 ◽  
Author(s):  
Mithun Prasad ◽  
Alicia Meza ◽  
Hyun J. Kim ◽  
Matthew S. Brown ◽  
Fereidoun Abtin ◽  
...  

Author(s):  
Burton B. Silver ◽  
Theodore Lawwill

Dutch-belted 1 to 2.5 kg anesthetized rabbits were exposed to either xenon or argon laser light administered in a broad band, designed to cover large areas of the retina. For laser exposure, the pupil was dilated with atropine sulfate 1% and pheny lephrine 10%. All of the laser generated power was within a band centered at 5145.0 Anstroms. Established threshold for 4 hour exposures to laser irradiation are in the order of 25-35 microwatts/cm2. Animals examined for ultrastructural changes received 4 hour threshold doses. These animals exhibited ERG, opthalmascopic, and histological changes consistent with threshold damage.One month following exposure the rabbits were killed with pentobarbitol. The eyes were immediately enucleated and dissected while bathed in 3% phosphate buffered gluteraldehyde.


Author(s):  
JS Deitch ◽  
KL Smith ◽  
JW Swann ◽  
JN Turner

Neurons labeled with horseradish peroxidase and reacted with diaminobenzidine (DAB) can be imaged using a confocal scanning laser microscope (CSLM) in the reflection mode. In contrast to fluorescent markers, the DAB reaction product is thought to be stable and can be observed by both light and electron microscopy. We have investigated the sensitivity of the DAB reaction product to laser irradiation, and present the spectrophotometric properties of DAB before and after exposure in the CSLM.Pyramidal neurons in slices of rat hippocampus were injected with biocytin (a biotin-lysine complex), fixed overnight in 4% paraformaldehyde, and vibratome sectioned at 75 μm. Biocytin was detected with avidin-HRP (1:200) in 0.5% Triton X-100, incubated in DAB (0.5 mg/ml) with or without 0.04% nickel ammonium sulfate (Ni), dehydrated, and imaged in a Bio Rad MRC-500 CSLM with an argon ion laser (488 and 514 nm). Spectrophotometric measurements of the soma were made on a Zeiss microspectrophotometer, as a function of laser exposure (100-1000 scans) and staining protocol.


1994 ◽  
Vol 71 (04) ◽  
pp. 499-506 ◽  
Author(s):  
Mark W C Hatton ◽  
Bonnie Ross-Ouellet

SummaryThe behavior of 125I-labeled recombinant hirudin towards the uninjured and de-endothelialized rabbit aorta wall has been studied in vitro and in vivo to determine its usefulness as an indicator of thrombin activity associated with the aorta wall. Thrombin adsorbed to either sulfopropyl-Sephadex or heparin-Sepharose bound >95% of 125I-r-hirudin and the complex remained bound to the matrix. Binding of 125I-r-hirudin to the exposed aorta subendothelium (intima-media) in vitro was increased substantially if the tissue was pre-treated with thrombin; the quantity of l25I-r-hirudin bound to the de-endothelialized intima-media (i.e. balloon-injured in vitro) correlated positively with the quantity of bound 131I-thrombin (p <0.01). Aortas balloon-injured in vivo were measured for thrombin release from, and binding of 125I-r-hirudin to, the de-endothelialized intimal surface in vitro; 125I-r-hirudin binding correlated with the amount of active thrombin released (p <0.001). Uptake of 125I-r-hirudin by the aorta wall in vivo was proportional to the uptake of 131I-fibrinogen (as an indicator of thrombin activity) before and after balloon injury. After 30 min in the circulation, specific 125I-r-hirudin binding to the uninjured and de-endo- thelialized (at 1.5 h after injury) aorta wall was equivalent to 3.4 (± 2.5) and 25.6 (±18.1) fmol of thrombin/cm2 of intima-media, respectively. Possibly, only hirudin-accessible, glycosaminoglycan-bound thrombin is measured in this way.


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