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Gold nanoparticles allow detection of early-stage edema in mice via computed tomography imaging.

ABSTRACT: Due to their high X-ray attenuation, gold nanoparticles (GNPs) emerged as preclinical contrast agents by giving high vasculature contrast. For this reason, GNPs are regularly applied for computed tomography (CT) imaging of tumors but not for the visualization of inflammation. The aim of this study was to evaluate the biocompatibility and applicability of preclinical GNPs (AuroVist™) of two different sizes (1.9 nm and 15 nm) for the detection of inflammation-associated phagocytes in early-stage edema. Both GNP variants were stable under in vitro conditions and achieved high micro-CT (mCT) contrast after embedment into agarose. Fifteen-nanometer GNPs were detected after uptake into macrophages via mCT imaging exhibiting higher X-ray contrast than cells treated with 1.9 nm GNPs and untreated ones. Both 1.9 nm and 15 nm GNPs exhibited good biocompatibility on murine macrophages according to ATP and cellular dehydrogenase levels. Reactive oxygen species levels produced by phagocytic cells decreased significantly (P?0.05) after co-incubation with GNPs regardless of the size of the nanoparticle (NP) in comparison to untreated control cells. In vivo mCT studies of inflammation imaging revealed that GNPs with a diameter of 15 nm accumulated within subcutaneous edema 2 hours after injection with a maximum signaling 8 hours postinjection and could be detected up to 48 hours within the edema region. In contrast, 1.9 nm GNPs were not shown to accumulate at the site of the inflammation region and were mostly excreted via the renal system 2-4 hours after injection. In conclusion, our study demonstrated that both GNP variants (1.9 nm and 15 nm) were stable and biocompatible under in vitro conditions. However, only 15 nm NPs have the potential as contrast agent for phagocyte labeling and applications in CT imaging of inflammation on a cellular level.

SUBMITTER: Domey J

PROVIDER: S-EPMC4459621 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Gold nanoparticles allow detection of early-stage edema in mice via computed tomography imaging.

Domey Jenny J Teichgräber Ulf U Hilger Ingrid I

International journal of nanomedicine 20150602

Due to their high X-ray attenuation, gold nanoparticles (GNPs) emerged as preclinical contrast agents by giving high vasculature contrast. For this reason, GNPs are regularly applied for computed tomography (CT) imaging of tumors but not for the visualization of inflammation. The aim of this study was to evaluate the biocompatibility and applicability of preclinical GNPs (AuroVist™) of two different sizes (1.9 nm and 15 nm) for the detection of inflammation-associated phagocytes in early-stage e ...[more]

PMID: 26082631

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Project description:BackgroundIn chronic obstructive pulmonary disease (COPD) abnormal lung function is related to emphysema and airway obstruction, but their relative contribution in each GOLD-stage is not fully understood. In this study, we used quantitative computed tomography (QCT) parameters for phenotyping of emphysema and airway abnormalities, and to investigate the relative contribution of QCT emphysema and airway parameters to airflow limitation specifically in each GOLD stage.MethodsNon-contrast computed tomography (CT) of 492 patients with COPD former GOLD 0 COPD and COPD stages GOLD 1-4 were evaluated using fully automated software for quantitative CT. Total lung volume (TLV), emphysema index (EI), mean lung density (MLD), and airway wall thickness (WT), total diameter (TD), lumen area (LA), and wall percentage (WP) were calculated for the entire lung, as well as for all lung lobes separately. Results from the 3rd-8th airway generation were aggregated (WT3-8, TD3-8, LA3-8, WP3-8). All subjects underwent whole-body plethysmography (FEV1%pred, VC, RV, TLC).ResultsEI was higher with increasing GOLD stages with 1.0 ± 1.8% in GOLD 0, 4.5 ± 9.9% in GOLD 1, 19.4 ± 15.8% in GOLD 2, 32.7 ± 13.4% in GOLD 3 and 41.4 ± 10.0% in GOLD 4 subjects (p < 0.001). WP3-8 showed no essential differences between GOLD 0 and GOLD 1, tended to be higher in GOLD 2 with 52.4 ± 7.2%, and was lower in GOLD 4 with 50.6 ± 5.9% (p = 0.010 - p = 0.960). In the upper lobes WP3-8 showed no significant differences between the GOLD stages (p = 0.824), while in the lower lobes the lowest WP3-8 was found in GOLD 0/1 with 49.9 ± 6.5%, while higher values were detected in GOLD 2 with 51.9 ± 6.4% and in GOLD 3/4 with 51.0 ± 6.0% (p < 0.05). In a multilinear regression analysis, the dependent variable FEV1%pred can be predicted by a combination of both the independent variables EI (p < 0.001) and WP3-8 (p < 0.001).ConclusionQCT parameters showed a significant increase of emphysema from GOLD 0-4 COPD. Airway changes showed a different spatial pattern with higher values of relative wall thickness in the lower lobes until GOLD 2 and subsequent lower values in GOLD3/4, whereas there were no significant differences in the upper lobes. Both, EI and WP5-8 are independently correlated with lung function decline.

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Gold nanoparticles allow detection of early-stage edema in mice via computed tomography imaging.

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Gold nanoparticles allow detection of early-stage edema in mice via computed tomography imaging.

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