Biosynthetic gas vesicles as a novel ultrasound contrast agent for diagnosing and treating myocardial infarction.

IF 13.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Theranostics Pub Date : 2025-07-28 eCollection Date: 2025-01-01 DOI:10.7150/thno.118543
Zihang Wang, Maierhaba Yibulayin, Kezhi Yu, Tingting Liu, Lina Guan, Baihetiya Tayier, Lingjie Yang, Shangke Chen, Yuming Mu, Fei Yan
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引用次数: 0

Abstract

Rationale: Myocardial contrast echocardiography (MCE) plays an important role in diagnosis of myocardial infarction (MI). However, its accuracy is limited by image quality because microbubble-based MCE produces negative contrast enhancement in the infarcted myocardial tissue. This study aimed to develop nanoscale gas vesicles (GVs) from Halobacteria NRC-1 (hGVs) and GV-expressing genetically engineered E. coli (eGVs) and compare their imaging performance with commercial Sonovue in MI rats. Methods: We developed nanoscale gas vesicles (GVs) from Halobacteria NRC-1 (hGVs) and GV-expressing genetically engineered E. coli (eGVs) and compared their imaging performance with Sonovue in MI rats. Unlike SF₆-filled Sonovue, GVs are air-filled protein nanobubbles with unique shapes. We used immunofluorescence and TEM to examine GVs' distribution in myocardial tissue and analyzed the mechanisms of their penetration into infarcted areas. Additionally, we evaluated the potential of oxygen delivery to ischemic myocardium using ultrasound-targeted bubble destruction. Results: hGVs produced significantly positive contrast enhancement and could last for a longer time in the infarcted area. Immunofluorescence and TEM examination confirmed that hGVs penetrated out the blood vessels into the ischemic myocardium and eGVs primarily retained around endothelial cells, while Sonovue could not pass through the damaged vessels. Mechanistic analysis revealed that inflammatory cytokines results in leaky blood vessels, facilitating the penetration of nanoscale GVs into the infarcted myocardial tissue. Moreover, hGVs exhibited excellent imaging performance across different pathological stages, especially during the inflammatory phase. More importantly, oxygen delivery into the ischemic myocardium through ultrasound-targeted bubble destruction technology greatly promoted the functional recovery of the ischemic myocardium. Conclusions: hGVs demonstrated superior imaging performance and penetration capabilities specifically at the myocardial infarction sites in rats.Their ability to provide positive contrast and deliver oxygen via ultrasound-targeted bubble destruction enables improved diagnosis and treatment of MI.

生物合成气体囊泡作为一种新型超声造影剂用于诊断和治疗心肌梗死。
理由:心肌超声造影(MCE)在心肌梗死(MI)的诊断中具有重要作用。然而,其准确性受到图像质量的限制,因为基于微泡的MCE在梗死心肌组织中产生负的对比度增强。本研究旨在从盐杆菌nfc -1 (hGVs)和表达gv的基因工程大肠杆菌(eGVs)中培养纳米级气体囊泡(GVs),并将其与商用Sonovue在心肌梗死大鼠中的成像性能进行比较。方法:从盐杆菌nfc -1 (hGVs)和表达gv的基因工程大肠杆菌(eGVs)中制备纳米级气体囊泡(GVs),并与Sonovue在心肌梗死大鼠中的成像性能进行比较。与SF货轮填充的Sonovue不同,gv是具有独特形状的充气蛋白质纳米气泡。利用免疫荧光和透射电镜观察了gv在心肌组织中的分布,并分析了其渗透梗死区的机制。此外,我们评估了潜在的氧气输送到缺血心肌使用超声靶向气泡破坏。结果:hGVs在梗死区产生明显的正增强,并能持续较长时间。免疫荧光和透射电镜检查证实,hgv穿过血管进入缺血心肌,egv主要保留在内皮细胞周围,而Sonovue不能穿过受损血管。机制分析表明,炎症细胞因子导致血管渗漏,促进纳米级gv渗透到梗死心肌组织。此外,hgv在不同病理阶段,尤其是炎症期均表现出良好的影像学表现。更重要的是,通过超声靶向破泡技术将氧输送到缺血心肌中,极大地促进了缺血心肌的功能恢复。结论:hgv在大鼠心肌梗死部位表现出优越的成像性能和穿透能力。它们能够提供阳性对比,并通过超声靶向气泡破坏输送氧气,从而改善心肌梗死的诊断和治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Theranostics
Theranostics MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
25.40
自引率
1.60%
发文量
433
审稿时长
1 months
期刊介绍: Theranostics serves as a pivotal platform for the exchange of clinical and scientific insights within the diagnostic and therapeutic molecular and nanomedicine community, along with allied professions engaged in integrating molecular imaging and therapy. As a multidisciplinary journal, Theranostics showcases innovative research articles spanning fields such as in vitro diagnostics and prognostics, in vivo molecular imaging, molecular therapeutics, image-guided therapy, biosensor technology, nanobiosensors, bioelectronics, system biology, translational medicine, point-of-care applications, and personalized medicine. Encouraging a broad spectrum of biomedical research with potential theranostic applications, the journal rigorously peer-reviews primary research, alongside publishing reviews, news, and commentary that aim to bridge the gap between the laboratory, clinic, and biotechnology industries.
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