Wang Zihang, Yibulayin Maierhaba, Yu Kezhi, Liu Tingting, Guan Lina, Tayier Baihetiya, Yang Lingjie, Chen Shangke, Mu Yuming, Yan Fei
Department of Echocardiography, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang Key Laboratory of Ultrasound Medicine, Xinjiang 830000, China.
State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
Theranostics. 2025 Jul 28;15(16):8553-8568. doi: 10.7150/thno.118543. eCollection 2025.
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 (hGVs) and GV-expressing genetically engineered (eGVs) and compare their imaging performance with commercial Sonovue in MI rats. We developed nanoscale gas vesicles (GVs) from (hGVs) and GV-expressing genetically engineered (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. 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. 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.
心肌对比超声心动图（MCE）在心肌梗死（MI）的诊断中起着重要作用。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性对比增强。本研究旨在从人源气体囊泡（hGVs）和表达气体囊泡的基因工程菌（eGVs）中开发纳米级气体囊泡（GVs），并在MI大鼠中比较它们与商用声诺维的成像性能。我们从人源气体囊泡（hGVs）和表达气体囊泡的基因工程菌（eGVs）中开发了纳米级气体囊泡（GVs），并在MI大鼠中比较它们与声诺维的成像性能。与填充六氟化硫的声诺维不同，GVs是具有独特形状的充气蛋白纳米气泡。我们使用免疫荧光和透射电子显微镜来检查GVs在心肌组织中的分布，并分析它们渗透到梗死区域的机制。此外，我们使用超声靶向微泡破坏技术评估了向缺血心肌输送氧气的潜力。hGVs在梗死区域产生了显著的正性对比增强，并且可以持续更长时间。免疫荧光和透射电子显微镜检查证实，hGVs穿透血管进入缺血心肌，而eGVs主要保留在内皮细胞周围，而声诺维无法穿过受损血管。机制分析表明，炎性细胞因子导致血管渗漏，促进纳米级GVs渗透到梗死心肌组织中。此外，hGVs在不同病理阶段均表现出优异的成像性能，尤其是在炎症期。更重要的是，通过超声靶向微泡破坏技术向缺血心肌输送氧气极大地促进了缺血心肌的功能恢复。hGVs在大鼠心肌梗死部位表现出卓越的成像性能和渗透能力。它们通过超声靶向微泡破坏提供正性对比和输送氧气的能力有助于改善MI的诊断和治疗。
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