Abstract：
Overactive or dysregulated cytokine expression is a hallmark of many acute and chronic inflammatory diseases. This is true for acute or chronic infections, neurodegenerative diseases, autoimmune diseases, cardiovascular diseases, cancer, and others. Cytokines such as interleukin-6 (IL-6) are known therapeutic targets and biomarkers for such inflammatory diseases. Platforms for cytokine detection are, therefore, desirable tools for both research and clinical applications. Single-walled carbon nanotubes (SWCNT) are versatile nanomaterials with near-infrared fluorescence that can serve as transducers for optical sensors. When functionalized with an analyte-specific recognition element, SWCNT emission may become sensitive and selective toward the desired target. SWCNT-aptamer sensors are easily assembled, inexpensive, and biocompatible. In this work, we introduced a nanosensor design based on SWCNT and a DNA aptamer specific to IL-6. We first evaluated several SWCNT-aptamer constructs based on this simple direct complexation method, wherein the aptamer both solubilizes the SWCNT and confers sensitivity to IL-6. The sensor limit of detection, 105 ng/mL, lies in the relevant range for pathological IL-6 levels. Upon investigation of sensor kinetics, we found rapid response within seconds of antigen addition which continued over the course of 3 h. We found that this sensor construct is stable and the aptamer is not displaced from the nanotube surface during IL-6 detection. Finally, we investigated the ability of this sensor construct to detect macrophage activation caused by bacterial lipopolysaccharides (LPS) in an in vitro model of disease, finding rapid and sensitive detection of macrophage-expressed IL-6. We are confident that further development of this sensor will have novel implications for diagnosis of acute and chronic inflammatory diseases, in addition to contributing to the understanding of the role of cytokines in these diseases.
摘要：
过度活跃或失调的细胞因子表达是许多急性和慢性炎性疾病的标志。急性或慢性感染都是如此，神经退行性疾病，自身免疫性疾病，心血管疾病,癌症,和其他人。细胞因子如白介素-6(IL-6)是此类炎性疾病的已知治疗靶标和生物标志物。细胞因子检测的平台是，因此,研究和临床应用的理想工具。单壁碳纳米管（SWCNT）是具有近红外荧光的多功能纳米材料，可用作光学传感器的换能器。当用分析物特异性识别元件功能化时，SWCNT发射可以变得对期望的靶敏感和选择性。SWCNT适体传感器易于组装，便宜,和生物相容性。在这项工作中,我们介绍了一种基于SWCNT和IL-6特异性DNA适体的纳米传感器设计。我们首先基于这种简单的直接复合方法评估了几种SWCNT适体构建体，其中适体既溶解SWCNT又赋予对IL-6的敏感性。传感器的检测极限，105ng/mL,位于病理性IL-6水平的相关范围内。在研究传感器动力学后，我们发现在持续3小时的过程的抗原添加数秒内的快速反应。我们发现该传感器构建体是稳定的,并且在IL-6检测期间适体不从纳米管表面移位。最后,我们研究了这种传感器构建体在体外疾病模型中检测细菌脂多糖（LPS）引起的巨噬细胞活化的能力，快速、灵敏地检测巨噬细胞表达的IL-6。我们相信，这种传感器的进一步发展将对急性和慢性炎症性疾病的诊断产生新的影响。除了有助于了解细胞因子在这些疾病中的作用。
