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基于靶标触发的碳点金属增强荧光的 HE4 生物标志物和卵巢癌细胞的荧光开启免疫传感。

Fluorescence turn-on immunosensing of HE4 biomarker and ovarian cancer cells based on target-triggered metal-enhanced fluorescence of carbon dots.

机构信息

School of Medical Imaging, Xuzhou Medical University, Xuzhou, 221004, China; Department of Radiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221004, China.

School of Medical Imaging, Xuzhou Medical University, Xuzhou, 221004, China.

出版信息

Anal Chim Acta. 2021 Dec 1;1187:339160. doi: 10.1016/j.aca.2021.339160. Epub 2021 Oct 11.

DOI:10.1016/j.aca.2021.339160
PMID:34753571
Abstract

Rapid and sensitive detection of tumor biomarkers and cancer cells is of crucial importance for the early diagnosis and prognosis prediction of cancer. The present report describes a target-induced fluorescence enhancement immunosensor that utilizes the optical property of carbon dots (CDs) and the metal-enhanced fluorescence effect (MEF) property of silver nanoparticles (AgNPs) for the sensitive detection of the cancer biomarker human epididymis protein 4 (HE4) and ovarian cancer cells. Nitrogen and sulfur co-doped CDs with a quantum yield of 85.6% were prepared and served as the fluorophore in MEF. The HE4 antibody (Ab) specific to the HE4 antigen was linked covalently to the surface of the synthesized CDs as the capture. The HE4 Ab-conjugated AgNPs (AgNPs-Ab) were prepared and utilized as signal amplification elements. In the presence of the target HE4, composite sandwich structures were formed between the labeled CDs-Ab and AgNPs-Ab, which brought the CDs and AgNPs into proximity, resulting in the fluorescence of CDs enhancement owing to MEF. The intensity of fluorescence enhancement was positively correlated with the HE4 concentration in the clinically important range of 0.01-200 nM with a limit detection of 2.3 pM. Moreover, the immunosensor was also successfully applied to specific fluorescence labeling and quantitative determination of HE4-positive ovarian cancer cells. The proposed target-triggered MEF sensor platform demonstrated high sensitivity, excellent anti-interference ability, along with successful validation in complex biological matrices, providing a new approach for HE4 detection in early diagnosis and therapeutic monitoring.

摘要

快速、灵敏地检测肿瘤标志物和癌细胞对于癌症的早期诊断和预后预测至关重要。本报告描述了一种基于靶标诱导的荧光增强免疫传感器,该传感器利用了碳点(CDs)的光学性质和银纳米粒子(AgNPs)的金属增强荧光效应(MEF)性质,用于灵敏检测癌症标志物人附睾蛋白 4(HE4)和卵巢癌细胞。制备了具有 85.6%量子产率的氮硫共掺杂 CDs,并将其用作 MEF 的荧光团。针对 HE4 抗原的 HE4 抗体(Ab)通过共价键连接到合成的 CDs 表面作为捕获。制备了 HE4 Ab 修饰的 AgNPs(AgNPs-Ab)并将其用作信号放大元件。在靶标 HE4 的存在下,标记的 CDs-Ab 和 AgNPs-Ab 之间形成了复合夹心结构,使 CDs 和 AgNPs 接近,从而由于 MEF 导致 CDs 荧光增强。荧光增强的强度与临床上重要的 0.01-200 nM 范围内的 HE4 浓度呈正相关,检出限为 2.3 pM。此外,该免疫传感器还成功应用于 HE4 阳性卵巢癌细胞的特异性荧光标记和定量测定。所提出的基于靶标触发的 MEF 传感器平台表现出高灵敏度、优异的抗干扰能力,并且在复杂的生物基质中得到了成功验证,为早期诊断和治疗监测中的 HE4 检测提供了一种新方法。

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