Department of Biomedical Engineering, The City College of New York, New York, New York 10031, United States.
PhD Program in Chemistry, Graduate Center, City University of New York, New York, New York 10016, United States.
ACS Sens. 2024 Jul 26;9(7):3697-3706. doi: 10.1021/acssensors.4c00887. Epub 2024 Jun 27.
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.
细胞因子表达过度或失调是许多急性和慢性炎症性疾病的标志。无论是急性还是慢性感染、神经退行性疾病、自身免疫性疾病、心血管疾病、癌症等，都是如此。白细胞介素 6（IL-6）等细胞因子是这些炎症性疾病的治疗靶点和生物标志物。因此，用于细胞因子检测的平台是研究和临床应用的理想工具。单壁碳纳米管（SWCNT）是一种多功能纳米材料，具有近红外荧光，可作为光传感器的换能器。当与分析物特异性识别元件功能化时，SWCNT 的发射可能对所需靶标变得敏感和选择性。SWCNT-适体传感器易于组装、成本低廉且生物相容性好。在这项工作中，我们引入了一种基于 SWCNT 和针对 IL-6 的 DNA 适体的纳米传感器设计。我们首先根据这种简单的直接络合方法评估了几种 SWCNT-适体构建体，其中适体既能溶解 SWCNT，又能赋予对 IL-6 的敏感性。传感器的检测限为 105ng/mL，处于病理 IL-6 水平的相关范围内。在对传感器动力学进行研究后，我们发现抗原加入后几秒钟内即可快速响应，并且在 3 小时的过程中持续响应。我们发现这种传感器结构稳定，在检测 IL-6 期间，适体不会从纳米管表面位移。最后，我们研究了这种传感器构建体在疾病体外模型中检测细菌脂多糖（LPS）引起的巨噬细胞激活的能力，发现对巨噬细胞表达的 IL-6 进行快速和敏感的检测。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，同时也有助于了解细胞因子在这些疾病中的作用。
