Department of Radiology, Pediatric Molecular Imaging, Molecular Imaging Program at Stanford, Stanford University, Stanford, California 94305.
Google Inc., Mountain View, California 94043.
Biointerphases. 2021 Feb 3;16(1):011008. doi: 10.1116/6.0000755.
Ferumoxytol nanoparticles are being used clinically for the treatment of anemia and molecular imaging in patients. It is well documented that while most patients tolerate ferumoxytol well, a small percentage of patients (i.e., 0.01%) develop severe allergic reactions. The purpose of our proof-of-concept study was to determine whether patients with or without hypersensitivity reactions have specific protein corona profiles around ferumoxytol nanoparticles. In a retrospective, institutional review board approved pilot study, we enrolled 13 pediatric patients (5 girls, 8 boys, mean age 16.9 ± 8.2 years) who received a ferumoxytol-enhanced magnetic resonance imaging and who did (group 1, n = 5) or did not (group 2, n = 8) develop an allergic reaction. Blood samples of these patients were incubated with ferumoxytol, and the formation of a hard protein corona around ferumoxytol nanoparticles was measured by dynamic light scattering, zeta potential, and liquid chromatography-mass spectrometry. We also performed in vitro immune response analyses to randomly selected coronas from each group. Our results provide preliminary evidence that ex vivo analysis of the biomolecular corona may provide useful and predictive information on the possibility of severe allergic reactions to ferumoxytol nanoparticles. In the future, patients with predisposition of an allergic reaction to ferumoxytol may be diagnosed based on the proteomic patterns of the corona around ferumoxytol in their blood sample.
铁氧体纳米颗粒目前正在临床用于治疗贫血和患者的分子成像。有充分的文献记载表明，虽然大多数患者对铁氧体纳米颗粒耐受良好，但仍有一小部分患者（即 0.01%）会发生严重的过敏反应。我们这项概念验证研究的目的是确定是否有过敏反应的患者与无过敏反应的患者的铁氧体纳米颗粒周围有特定的蛋白质外壳特征。在一项回顾性的、机构审查委员会批准的试点研究中，我们纳入了 13 名接受铁氧体增强磁共振成像检查的儿科患者（5 名女性，8 名男性，平均年龄 16.9±8.2 岁），他们（第 1 组，n=5）或没有（第 2 组，n=8）发生过敏反应。这些患者的血液样本与铁氧体纳米颗粒孵育，并通过动态光散射、zeta 电位和液相色谱-质谱法测量铁氧体纳米颗粒周围形成的硬蛋白质外壳。我们还对来自每个组的随机选择的外壳进行了体外免疫反应分析。我们的结果初步证明，生物分子外壳的体外分析可能为铁氧体纳米颗粒发生严重过敏反应的可能性提供有用的预测信息。将来，对铁氧体纳米颗粒过敏反应有倾向的患者可能可以基于其血液样本中铁氧体周围的冠状蛋白质组学模式来进行诊断。
