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  3. Highly sensitive magnetic particle imaging of abdominal aortic aneurysm NETosis with anti-Ly6G iron oxide nanoparticles

Highly sensitive magnetic particle imaging of abdominal aortic aneurysm NETosis with anti-Ly6G iron oxide nanoparticles

  • Cell Death Discov. 2024 Sep 5;10(1):395. doi: 10.1038/s41420-024-02156-3.
Heng Wang # 1,  Ruijing Zhang # 2,  Xiaohua Jia # 3 4,  Siqi Gao 1,  Tingting Gao 1,  Keyi Fan 1,  Yaling Li 1,  Shule Wang 1,  Maolin Qiao 1,  Sheng Yan 1,  Hui Hui 5 6,  Honglin Dong 7
Affiliations

Affiliations

  • 1 Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, China.
  • 2 Department of Nephrology, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, China.
  • 3 Key Laboratory of Molecular Imaging of Chinese Academy of Sciences, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China.
  • 4 Department of Ultrasound, Shuozhou Grand Hospital of Shanxi Medical University, Shuozhou, 036000, China.
  • 5 Key Laboratory of Molecular Imaging of Chinese Academy of Sciences, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China. hui.hui@ia.ac.cn.
  • 6 National Key Laboratory of Kidney Diseases, Beijing, 100853, China. hui.hui@ia.ac.cn.
  • 7 Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, China. honglindong@sxmu.edu.cn.
  • # Contributed equally.
PMID: 39237520 DOI: 10.1038/s41420-024-02156-3
Abstract

Abdominal aortic aneurysms (AAA) are a significant health concern in developed countries due to their considerable mortality rate. The crucial factor of the progression of AAA is the release of neutrophils and neutrophil extracellular traps (NETs). Magnetic particle imaging (MPI) is a new imaging technique that offers the capability to detect superparamagnetic iron oxide nanoparticles (SPION) with exceptional sensitivity. We aimed to investigate the functional imaging of MPI for the detection and monitoring of neutrophil infiltration within AAA. A novel multimodal imaging agent targeting neutrophils, PEG-Fe3O4-Ly6G-Cy7 nanoparticles (Ly6G NPs), were designed by coupling Fe3O4 nanoparticles with Ly6G Antibodies and Cy7. The targeting and sensitivity of Ly6G NPs were assessed using MPI and fluorescence imaging (FLI) in the AAA mouse model. After the inhibition of NETosis, the degree of neutrophil infiltration and AAA severity were assessed using MPI with Ly6G NPs. Ly6G NPs accurately localized and quantitatively analyzed AAA lesion sites in mice using MPI/FLI/CT. Compared to the control group, elevated MPI and FLI signal intensities were detected at the abdominal aortic lesion site, and neutrophil infiltration and NETs accumulation were detected by histological analysis in the AAA models. After the inhibition of NETs accumulation in vivo, pathological damage in the abdominal aorta was significantly reduced, along with a decrease in the accumulation of Ly6G NPs and MPI signals. This multimodal MPI strategy revealed that nanoparticles targeting Ly6G can be used to detect neutrophil infiltration within AAA and monitor AAA severity.

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