利用抗 Ly6G 氧化铁纳米粒子对腹主动脉瘤 NETosis 进行高灵敏度磁粒子成像。

IF 6.1 2区 生物学 Q1 CELL BIOLOGY Cell Death Discovery Pub Date : 2024-09-05 DOI:10.1038/s41420-024-02156-3
Heng Wang, Ruijing Zhang, Xiaohua Jia, Siqi Gao, Tingting Gao, Keyi Fan, Yaling Li, Shule Wang, Maolin Qiao, Sheng Yan, Hui Hui, Honglin Dong
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引用次数: 0

摘要

在发达国家,腹主动脉瘤(AAA)因其相当高的死亡率而成为一个重大的健康问题。AAA 进展的关键因素是中性粒细胞和中性粒细胞胞外捕获物(NET)的释放。磁粉成像(MPI)是一种新的成像技术,能以极高的灵敏度检测超顺磁性氧化铁纳米粒子(SPION)。我们的目的是研究 MPI 在检测和监测 AAA 内中性粒细胞浸润方面的功能成像。通过将Fe3O4纳米颗粒与Ly6G抗体和Cy7结合,我们设计出了一种靶向中性粒细胞的新型多模态成像剂--PEG-Fe3O4-Ly6G-Cy7纳米颗粒(Ly6G NPs)。在 AAA 小鼠模型中使用 MPI 和荧光成像(FLI)评估了 Ly6G NPs 的靶向性和敏感性。抑制NETosis后,使用Ly6G NPs的MPI评估了中性粒细胞的浸润程度和AAA的严重程度。利用MPI/FLI/CT,Ly6G NPs能准确定位并定量分析小鼠的AAA病变部位。与对照组相比,腹主动脉病变部位的 MPI 和 FLI 信号强度升高,组织学分析检测到 AAA 模型中有中性粒细胞浸润和 NETs 聚集。在体内抑制NETs聚集后,腹主动脉的病理损伤明显减轻,Ly6G NPs和MPI信号的聚集也有所减少。这种多模态MPI策略揭示了靶向Ly6G的纳米颗粒可用于检测AAA内的中性粒细胞浸润并监测AAA的严重程度。
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Highly sensitive magnetic particle imaging of abdominal aortic aneurysm NETosis with anti-Ly6G iron oxide nanoparticles.

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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来源期刊
Cell Death Discovery
Cell Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology
CiteScore
8.30
自引率
1.40%
发文量
468
审稿时长
9 weeks
期刊介绍: Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary. Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.
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