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Noninvasive imaging of the lung NETosis by anti-Ly6G iron oxide nanoparticles.

ABSTRACT: It is challenging to visualize noninvasively the formation of neutrophil extracellular traps, known as NETosis, and therefore difficult to monitor disease progression. A desirable molecular imaging probe is the iron oxide nanoparticle (NP) that could induce reactive oxygen species. Here, we used C57BL/6 mice with pristane-induced lupus, which mimics systemic lupus erythematosus. Administration of anti-Ly6G antibody-conjugated NP allowed detection of NETosis with fluorescent molecular imaging, as evidenced by flow cytometric analysis of citrullinated histone H3 expression in lung neutrophils. This finding was consistent with NP-induced blood NETosis in a spontaneous lupus model of B6.MRL-lpr mice. A chronic assessment was performed in which the lupus mice were protected from enhanced oxidative burst by anti-Ly6G NP. This NP can migrate from the peritoneal cavity to the lungs, as visualized by magnetic particle imaging. Overall, our study provides evidence for a highly sensitive assessment of NETosis in lupus through magnetic particle imaging.

SUBMITTER: Zhong J

PROVIDER: S-EPMC9382280 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Noninvasive imaging of the lung NETosis by anti-Ly6G iron oxide nanoparticles.

Zhong Jianghong J Zheng Chanyu C Gao Haiqiang H Tong Wei W Hui Hui H Tian Jie J

Heliyon 20220803 8

It is challenging to visualize noninvasively the formation of neutrophil extracellular traps, known as NETosis, and therefore difficult to monitor disease progression. A desirable molecular imaging probe is the iron oxide nanoparticle (NP) that could induce reactive oxygen species. Here, we used C57BL/6 mice with pristane-induced lupus, which mimics systemic lupus erythematosus. Administration of anti-Ly6G antibody-conjugated NP allowed detection of NETosis with fluorescent molecular imaging, as ...[more]

PMID: 35991979

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Project description:BackgroundThe use of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles to visualize cells has been applied clinically, showing the potential for monitoring cells in vivo with magnetic resonance imaging (MRI). USPIO conjugated with anti-CD133 antibodies (USPIO-CD133 Ab) that recognize the CD133 molecule, a cancer stem cell marker in a variety of cancers, was studied as a novel and potent agent for MRI contrast enhancement of tumor cells.Materials and methodsAnti-CD133 antibodies were used to conjugate with USPIO via interaction of streptavidin and biotin for in vivo labeling of CD133-positive cells in xenografted tumors and N-ethyl-N-nitrosourea (ENU)-induced brain tumors. The specific binding of USPIO-CD133 Ab to CD133-positive tumor cells was subsequently detected by Prussian blue staining and MRI with T2-weighted, gradient echo and multiple echo recombined gradient echo images. In addition, the cellular toxicity of USPIO-CD133 Ab was determined by analyzing cell proliferation, apoptosis, and reactive oxygen species production.ResultsUSPIO-CD133 Ab specifically recognizes in vitro and labels CD133-positive cells, as validated using Prussian blue staining and MRI. The assays of cell proliferation, apoptosis, and reactive oxygen species production showed no significant differences in tumor cells with or without labeling of USPIO-CD133 Ab. In vivo imaging of CD133-positive cells was demonstrated by intravenous injection of USPIO-CD133 Ab in mice with HT29 xenografted tumors. The MRI of HT29 xenografts showed several clusters of hypotensive regions that correlated with CD133 expression and Prussian blue staining for iron. In rat, brain tumors induced by transplacental ENU mutagenesis, several clusters of hypointensive zones were observed in CD133-expressing brain tumors by MRI and intravenously administered USPIO-CD133 Ab.ConclusionCombination of USPIO-CD133 Ab and MRI is valuable in recognizing CD133-expressing tumor cells in vitro, extracellularly labeling for cell tracking and detecting CD133-expressing tumors in xenografted tumors as well as ENU-induced rat brain tumors.

Dataset Information

Noninvasive imaging of the lung NETosis by anti-Ly6G iron oxide nanoparticles.

Publications

Noninvasive imaging of the lung NETosis by anti-Ly6G iron oxide nanoparticles.

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