Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil.
LIM44-Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo,São Paulo 01246-903, Brazil.
Molecules. 2020 Feb 11;25(4):765. doi: 10.3390/molecules25040765.
This in vitro study aimed to find the best method of granulocyte isolation for subsequentlabeling with multimodal nanoparticles (magnetic and fluorescent properties) to enable detectionby optical and magnetic resonance imaging (MRI) techniques. The granulocytes were obtained fromvenous blood samples from 12 healthy volunteers. To achieve high purity and yield, four differentmethods of granulocyte isolation were evaluated. The isolated granulocytes were labeled withmultimodal superparamagnetic iron oxide nanoparticles (M-SPIONs) coated with dextran, and theiron load was evaluated qualitatively and quantitatively by MRI, near-infrared fluorescence (NIRF)and inductively coupled plasma mass spectrometry (ICP-MS). The best method of granulocyteisolation was Percoll with Ficoll, which showed 95.92% purity and 94% viability. After labeling withM-SPIONs, the granulocytes showed 98.0% purity with a yield of 3.5 × 106 cells/mL and more than98.6% viability. The iron-loading value in the labeled granulocytes, as obtained by MRI, was 6.40 ±0.18 pg/cell. Similar values were found with the ICP-MS and NIRF imaging techniques. Therefore,our study shows that it is possible to isolate granulocytes with high purity and yield and labelingwith M-SPIONs provides a high internalized iron load and low toxicity to cells. Therefore, these MSPION-labeled granulocytes could be a promising candidate for future use ininflammation/infection detection by optical and MRI techniques.
这项体外研究旨在寻找最佳的粒细胞分离方法,以便随后用多模态纳米粒子(具有磁性和荧光特性)进行标记,从而能够通过光学和磁共振成像(MRI)技术进行检测。粒细胞从 12 名健康志愿者的静脉血样本中获得。为了实现高纯度和高产量,评估了四种不同的粒细胞分离方法。分离的粒细胞用葡聚糖包被的多模态超顺磁性氧化铁纳米粒子(M-SPION)进行标记,并通过 MRI、近红外荧光(NIRF)和电感耦合等离子体质谱(ICP-MS)定性和定量评估其铁载量。最佳的粒细胞分离方法是用葡聚糖包被的聚蔗糖(Percoll with Ficoll),其纯度达到 95.92%,活率达到 94%。用 M-SPION 标记后,粒细胞的纯度达到 98.0%,产量为 3.5×106 个细胞/mL,活率超过 98.6%。通过 MRI 获得的标记粒细胞的铁载量为 6.40±0.18pg/细胞。通过 ICP-MS 和 NIRF 成像技术也得到了类似的值。因此,我们的研究表明,用高纯度和高产量分离粒细胞并对其进行 M-SPION 标记是可行的,这可以提供高的内化铁负载和低的细胞毒性。因此,这些 M-SPION 标记的粒细胞可能是未来通过光学和 MRI 技术检测炎症/感染的有前途的候选物。