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基于环保合成金纳米粒子的用于癌胚抗原(CEA)和山古治肉瘤病毒癌基因同源物 1(YES1)等癌症生物标志物的超灵敏免疫传感器的多重检测。

Ultrasensitive immunosensor for multiplex detection of cancer biomarkers carcinoembryonic antigen (CEA) and yamaguchi sarcoma viral oncogene homolog 1 (YES1) based on eco-friendly synthesized gold nanoparticles.

机构信息

Program in Solid Tumors, Centro de Investigación Médica Aplicada (CIMA), University of Navarra, 31008, Pamplona, Spain; Department of Chemistry, University of Nairobi, 30197-00100, Nairobi, Kenya; School of Chemistry and Material Science, The Technical University of Kenya, 52428-00200, Nairobi, Kenya.

Department of Chemistry, University of Nairobi, 30197-00100, Nairobi, Kenya.

出版信息

Talanta. 2024 Jan 1;266(Pt 1):124934. doi: 10.1016/j.talanta.2023.124934. Epub 2023 Jul 13.

DOI:10.1016/j.talanta.2023.124934
PMID:37454512
Abstract

Cancer is one of the most extensive diseases with the highest mortality rate, accounting for almost 10 million deaths in 2020. The most common cancers are breast, lung, colon and rectum and prostate cancers. Of these, lung cancer, accounted for about 1.8 million of all cancer deaths (25%) in 2020. Detection of cancer relies on presence of biomarkers such as DNA molecules, proteins and metabolites released by cancerous cells into the circulation. Carcinoembryonic antigen (CEA) is one of the biomarkers that has been used for the detection of lung cancer. However, CEA is not specific to lung cancer since it is also manifested in gastric cancer, pancreatic cancer, colorectal cancer, and breast cancer. Recently, v-YES1 Yamaguchi sarcoma viral oncogene homolog 1 (YES1) was described as a specific biomarker for lung cancer. The detection of both CEA and YES1 would give more precise and authentic information for detecting lung cancer. This is because detection of a single tumor marker usually limits the precision in tumor diagnosis, due to the fact that several cancers have more than one marker linked with their prevalence. Whereas traditional methods have been used for the detection of CEA, electrochemical immunosensors have attracted considerable attention owing to their profound advantages, including fast response, miniaturization, high selectivity, low sample requirements and magnificent sensitivity. The fabrication of a multiplex and simultaneous immunosensor is met with challenge of preparation of distinguishable immunoprobes with different redox activities. This can be addressed by incorporation of electroactive Nano metals into the sensing platform. In this study, gold nanoparticles were used for the fabrication of an ultrasensitive sandwich electrochemical multiplex immunosensor for simultaneous detection of CEA and YES1. Under optimized conditions, the electrochemical immunosensor detection limit for YES1 and CEA was found to be 0.0022 and 0.0034 ng/mL respectively within a linear range of 0.1-50 ng/mL. The proposed immunosensor proved to be stable for up to 2 weeks and had negligible cross reactivity towards various interfering compounds in human plasma. This study reports that gold nanoparticles can be bio synthesized using shade dried Mangifera indica leaves extract. The bio-synthesized gold nanoparticles coupled with thiolated protein G can be used for fabrication of a multiplex immunosensor for detection of CEA and YES1. The proposed immunosensor can provide a new approach for early diagnosis of circulating cancer biomarkers and holds great promise for application in clinical diagnosis.

摘要

癌症是最广泛的疾病之一,死亡率最高,占 2020 年近 1000 万人死亡。最常见的癌症是乳腺癌、肺癌、结肠癌和直肠癌以及前列腺癌。其中,肺癌占 2020 年所有癌症死亡人数(25%)的 180 万左右。癌症的检测依赖于生物标志物的存在,如癌细胞释放到循环中的 DNA 分子、蛋白质和代谢物。癌胚抗原(CEA)是用于检测肺癌的生物标志物之一。然而,CEA 并不特异于肺癌,因为它也在胃癌、胰腺癌、结直肠癌和乳腺癌中表现出来。最近,v-YES1 山口肉瘤病毒癌基因同源物 1(YES1)被描述为肺癌的特异性生物标志物。检测 CEA 和 YES1 会提供更精确和真实的信息,用于检测肺癌。这是因为由于几种癌症都有一个以上与它们的流行相关的标志物,因此单一肿瘤标志物的检测通常会限制肿瘤诊断的准确性。虽然已经使用传统方法来检测 CEA,但电化学免疫传感器由于其快速响应、小型化、高选择性、低样品要求和出色的灵敏度等深刻优势而引起了相当大的关注。然而,由于具有不同氧化还原活性的免疫探针的制备具有挑战性,因此制备多重和同时的免疫传感器具有挑战性。这可以通过将电活性纳米金属掺入传感平台来解决。在这项研究中,使用金纳米粒子制备了用于同时检测 CEA 和 YES1 的超灵敏三明治电化学多重免疫传感器。在优化条件下,电化学免疫传感器对 YES1 和 CEA 的检测限分别为 0.0022 和 0.0034 ng/mL,线性范围为 0.1-50 ng/mL。该免疫传感器在长达 2 周的时间内表现稳定,并且对人血浆中的各种干扰化合物几乎没有交叉反应性。这项研究表明,金纳米粒子可以使用遮荫干燥的芒果叶提取物进行生物合成。与巯基化蛋白 G 偶联的生物合成金纳米粒子可用于制备用于检测 CEA 和 YES1 的多重免疫传感器。该免疫传感器可以为循环癌症生物标志物的早期诊断提供一种新方法,在临床诊断中具有很大的应用前景。

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