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具有中性粒细胞膜伪装的治疗性纳米颗粒在靶向动脉粥样硬化炎症斑块中的应用。

Application of therapeutical nanoparticles with neutrophil membrane camouflaging for inflammatory plaques targeting against atherosclerosis.

作者信息

Zhang Ningnannan, Zhang Tianzhu, Feng Jintang, Shang Jian, Zhang Beibei, Dong Qingyang, Zhang Zhang, Sun Chunyang

机构信息

Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, 300052, PR China.

Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450002, PR China.

出版信息

Mater Today Bio. 2024 Dec 10;30:101397. doi: 10.1016/j.mtbio.2024.101397. eCollection 2025 Feb.

Abstract

Atherosclerosis is the leading cause of cardiovascular disease and myocardial infarction. Precise and effective plaque targeting is a major objective for therapeutic outcomes throughout various stages of atherosclerosis. Inspired by the natural recruitment of neutrophils in atherosclerotic plaques, we fabricated a simvastatin (ST)-loaded and neutrophil membrane-cloaked nanoplatform (NNP) for enhancing localized payload delivery and atherosclerosis management. The resulting NNP mimicked neutrophil function and significantly decreased macrophage-mediated phagocytosis to prolong its own circulation time in the blood. Compared to pristine nanoparticles (NP) without a membrane coating, NNP achieved better plaque targeting in ApoE mice, as indicated by neutrophils actively recruited in atherosclerotic lesions. The higher plaque homing with NNP was monitored by dynamic fluorescence/magnetic resonance (MR) dual-modality imaging. The results further showed that NNP efficiently prevented atherosclerosis development mainly by suppressing local inflammatory macrophages, and the percentage of plaques in the entire aortic area was reduced to 4.75 ± 1.48 % following NNP treatment. A biosafety assessment indicated that the biomimetic NNP induced no noticeable toxicity in the body. This approach of neutrophil membrane-camouflaged nanoparticles offers new opportunities to various therapeutic agents for on-demand delivery in neutrophil-involved inflammatory diseases.

摘要

动脉粥样硬化是心血管疾病和心肌梗死的主要原因。在动脉粥样硬化的各个阶段,精确有效的斑块靶向是治疗效果的主要目标。受动脉粥样硬化斑块中中性粒细胞自然募集的启发,我们制备了一种负载辛伐他汀(ST)并包裹中性粒细胞膜的纳米平台(NNP),以增强局部有效载荷递送和动脉粥样硬化管理。所得的NNP模拟了中性粒细胞的功能,并显著降低了巨噬细胞介导的吞噬作用,从而延长了其在血液中的循环时间。与没有膜包被的原始纳米颗粒(NP)相比,NNP在ApoE小鼠中实现了更好的斑块靶向,动脉粥样硬化病变中积极募集的中性粒细胞表明了这一点。通过动态荧光/磁共振(MR)双模态成像监测到NNP具有更高的斑块归巢性。结果进一步表明,NNP主要通过抑制局部炎性巨噬细胞有效预防了动脉粥样硬化的发展,NNP治疗后整个主动脉区域的斑块百分比降至4.75±1.48%。生物安全性评估表明,仿生NNP在体内未诱导明显的毒性。这种中性粒细胞膜伪装纳米颗粒的方法为各种治疗药物在涉及中性粒细胞的炎症性疾病中按需递送提供了新的机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d88/11722182/f7e458ee70b0/sc1.jpg

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