Designing S100A9-Targeted Plant Virus Nanoparticles to Target Deep Vein Thrombosis.

Designing S100A9-Targeted Plant Virus Nanoparticles to Target Deep Vein Thrombosis.
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DOI:
10.1021/acs.biomac.1c00303
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发表时间:
2021-06-14
期刊:
影响因子:
6.2
通讯作者:
Steinmetz, Nicole F.
Steinmetz, Nicole F.
中科院分区:
化学2区
文献类型:
--
作者:
Park, Jooneon;Wen, Amy M.;Gao, Huiyun;Shin, Matthew D.;Simon, Daniel, I;Wang, Yunmei;Steinmetz, Nicole F.

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血栓栓塞病症是全球范围内死亡的主要原因,并且深静脉血栓形成(DVT)或闭塞性静脉凝块形成是导致重要器官损伤、长期并发症和危及生命的病症(诸如肺栓塞)的关键且日益严重的问题。早期诊断和治疗与良好的预后相关。然而,这些领域的现有技术,如用于诊断的超声检查和用于治疗的抗凝剂,在准确性和治疗窗口方面受到限制。在这项工作中,我们研究了使用基于植物病毒的纳米颗粒载体靶向骨髓相关蛋白14(MRP-14,也称为S100 A9)作为实现组织特异性的手段,以帮助预后和治疗干预。我们使用组合肽库筛选来鉴定结合MRP-14的肽配体。通过使用豇豆花叶病毒(CPMV)和烟草花叶病毒(TMV)选择候选物并配制成纳米颗粒。我们的MRP-14靶向纳米颗粒在DVT小鼠模型中的血管内递送导致血栓中的积聚增强和血栓尺寸减小,表明纳米颗粒用于MRP-14的分子靶向的应用可能是改善DVT诊断、治疗和预后的有希望的方向。
Thromboembolic conditions are a leading cause of death worldwide, and deep vein thrombosis (DVT), or occlusive venous clot formation, is a critical and rising problem that contributes to damage of vital organs, long-term complications, and life-threatening conditions such as pulmonary embolism. Early diagnosis and treatment are correlated to better prognosis. However, current technologies in these areas, such as ultrasonography for diagnostics and anticoagulants for treatment, are limited in terms of their accuracy and therapeutic windows. In this work, we investigated targeting myeloid related protein 14 (MRP-14, also known as S100A9) using plant virus-based nanoparticle carriers as a means to achieve tissue specificity aiding prognosis and therapeutic intervention. We used a combinatorial peptide library screen to identify peptide ligands that bind MRP-14. Candidates were selected and formulated as nanoparticles by using cowpea mosaic virus (CPMV) and tobacco mosaic virus (TMV). Intravascular delivery of our MRP-14-targeted nanoparticles in a murine model of DVT resulted in enhanced accumulation in the thrombi and reduced thrombus size, suggesting application of nanoparticles for molecular targeting of MRP-14 could be a promising direction for improving DVT diagnostics, therapeutics, and therefore prognosis.
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