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首页> 外文期刊>Materials science & engineering >Hemocompatibility of gallium-68 labeled iron oxide nanoparticles coated with 2,3-dicarboxypropane-1,1-diphosphonic acid
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Hemocompatibility of gallium-68 labeled iron oxide nanoparticles coated with 2,3-dicarboxypropane-1,1-diphosphonic acid

机译：镓-68标记的氧化铁纳米颗粒的血液相色涂有2,3-二羧丙烷-1,1-二膦酸的氧化铁纳米颗粒

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摘要

Dual-modality contrast agents (DMCA), such as radiolabeled magnetic nanoparticles, have attracted significant attention in diagnostic applications due to their potency for the timely and accurate diagnosis of diseases. The hemocompatibility of a candidate DMCA with human blood is essential for the investigation of its application in vivo. In this respect, here we focused on the evaluation of the hemocompatibility of a new DMCA, that is based on iron oxide nanoparticles (i.e. Fe3O4 magnetite), with human red blood cells (RBCs). The specific iron oxide nanoparticles are surface functionalized with 2,3-dicarboxypropane-1,1-diphosphonic acid (-DPD) and radiolabeled with gallium-68 (Ga-68), resulting in Ga-68-DPD-Fe3O4. RBCs of five healthy individuals are incubated at room temperature for 120 min without and with Ga-68-DPD-Fe3O4 at concentrations 0.1 and 1.0 mg/ml. Optical microscopy (OM) and atomic force microscopy (AFM) are employed to assess detailed information on the overall morphological and geometrical characteristics of the entire cell at the microscopic (10(-6) m) level and on the membrane morphology at the nanoscopic (10(-9) m) level. In addition, a standard hematology analyzer (HA) is used to obtain complete blood count information.At the microscopic level, the combined OM, AFM and HA data revealed that the overall shape/size characteristics of RBCs were preserved upon incubation with Ga-68-DPD-Fe3O4 . However, at the nanoscopic level, the AFM results revealed two different kinds of local deconstructions of the RBCs membrane, termed holes and ulcerlike abnormalities, that were observed in both the DMCA-free and DMCA-incubated samples. Holes did not exhibit any statistically significant difference upon incubation with the Ga-68-DPD-Fe3O4 DMCA. On the contrary, ulcer-like abnormalities exhibited two statistically significant differences upon incubation with the Ga-68-DPD-Fe3O4 DMCA. First, increased percentage of RBCs having at least one ulcer-like abnormality; in DMCA-incubated samples 78.6 +/- 11.6% for C-DMCA = 0.1 mg/ml and 80.4 +/- 11.1% for C-DMCA = 1.0 mg/ml, while in DMCA-free samples 61.2 +/- 8.4% prior to and 63.6 +/- 13.5% after incubation. Second, increased number of ulcer-like abnormalities per RBC; in DMCA-incubated samples 4.26 +/- 0.62 for C-DMCA = 0.1 mg/ml and 3.99 +/- 0.97 for C-DMCA = 1.0 mg/ml, while in DMCA-free samples 2.84 +/- 0.54 prior to and 2.98 +/- 0.50 after incubation. The combined OM, AFM and HA results prove fair hemocompatibility of the Ga-68-DPD-Fe3O4 DMCA with human RBCs, thus documenting its potential use in imaging applications.
机译：由于它们的效力及时诊断疾病的效力，双模态造影剂（DMCA）（如放射性标记磁性纳米粒子）引起了诊断应用的显着关注。候选DMCA与人类血液的血液相容性对于对体内施用的研究至关重要。在这方面，在这里，我们专注于评估新DMCA的血液相位性，其基于氧化铁纳米颗粒（即Fe3O4磁铁矿），具有人红细胞（RBC）。特定的氧化铁纳米颗粒是用2,3-二羧丙烷-1,1-二膦酸（-DPD）官能化的表面，并用镓-68（GA-68）放射性标记，得到GA-68-DPD-Fe3O4。将5个健康个体的RBC在室温下在室温下孵育120分钟，浓度为0.1和1.0mg / ml，在GA-68-DPD-Fe 3 O 4下孵育120分钟。使用光学显微镜（OM）和原子力显微镜（AFM）来评估微观（10（-6）m）水平的整个细胞的整体形态学和几何特征的详细信息，以及纳米镜的膜形态（ 10（-9）m）水平。此外，标准血液学分析仪（HA）用于获得完整的血液计数信息。显微级，组合的OM，AFM和HA数据显示，在与GA-68孵育时，RBC的整体形状/尺寸特性被保存-dpd-fe3o4。然而，在纳米镜水平下，AFM结果揭示了在无DMCA和DMCA-孵育的样品中观察到的RBCS膜，称为孔和溃疡异常的两种不同种类的局部解构。孔在与GA-68-DPD-FE3O4 DMCA孵育时没有表现出任何统计学上的差异。相反，溃疡状异常在与Ga-68-DPD-Fe3O4 DMCA孵育时表现出两种统计学显着的差异。首先，增加具有至少一种溃疡异常的RBC百分比;在DMCA孵育的样品中对于C-DMCA = 0.1mg / ml和80.4 +/- 11.6％的C-DMCA = 1.0mg / ml，而在无DMCA样品中，在DMCA的样品中之前的61.2 +/- 8.4％孵化后至63.6 +/- 13.5％。第二，每RBC的溃疡样异常数增加;在DMCA - 培养的样品中4.26 +/- 0.62用于C-DMCA = 0.1mg / ml和3.99 +/- 0.97，用于C-DMCA = 1.0mg / ml，而在无DMCA的样品中，在DMCA样品中2.84 +/- 0.54，在2.98之前孵化后+/- 0.50。组合的OM，AFM和HA结果证明了GA-68-DPD-FE3O4DMCA与人RBC的公平血液相色，从而记录其在成像应用中的潜在用途。

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