Institute for Advanced Materials, School of Materials Science and Engineering, Jiangsu University, Zhenjiang, 212013, PR China.
Department of Pulmonary and Critical Care Medicine, Yixing Hospital Affiliated to Jiangsu University, Yixing, 214200, PR China.
Anal Chim Acta. 2024 Feb 8;1289:342214. doi: 10.1016/j.aca.2024.342214. Epub 2024 Jan 3.
The detection of melanoma circulating biomarker in liquid biopsies is current under evaluation for being potentially utilized for earlier cancer diagnosis and its metastasis. Herein, we developed a non-invasive electrochemical approach for ultrasensitive detection of the S100B, serving as a potential promising blood circulating biomarker of melanoma, based on an aggregation-induced signal amplification (AISA) strategy via in-situ peptide self-assembly. The fundamental principle of this assay is that the designed amphiphilic peptides (C-Pep-Fc), fulfilling multiple functions, feature both a recognition region for specific binding to S100B and an aggregation (self-assembly) region for the formation of peptide nanomicelles under mild conditions. The C tails were encapsulated within the hydrophobic core of the aggregates, while the relatively hydrophilic recognition fragment Pep and Fc tag were exposed on the outer surface for subsequent recognition of S100B and signal output. AISA provided remarkable accumulation of electroactive Fc moieties that enabled ultrasensitive S100B detection of as low as 0.02 nM, which was 10-fold lower than un-amplified approach and better than previously reported assays. As a proof-of-concept study, further experiments also highlighted the good reproducibility and stability of AISA and demonstrated its usability when applied to simulated serum samples. Hence, this work not only presented a valuable assay tool for ultrasensitive detecting protein biomarker, but also advocated for the utilization of aggregation-induced signal amplification in electrochemical biosensing system, given its considerable potential for future practical applications.
在液体活检中检测黑色素瘤循环生物标志物目前正在评估中，有望用于更早地诊断癌症及其转移。在此，我们开发了一种非侵入性电化学方法，用于超灵敏检测 S100B，S100B 是一种有前途的黑色素瘤潜在循环生物标志物，该方法基于通过原位肽自组装的聚集诱导信号放大 (AISA) 策略。该测定的基本原理是，所设计的两亲肽（C-Pep-Fc）具有多种功能，其特征在于用于与 S100B 特异性结合的识别区域，以及在温和条件下形成肽纳米胶束的聚集（自组装）区域。C 尾被包含在聚集体的疏水性核心内，而相对亲水的识别片段 Pep 和 Fc 标签暴露在外部表面上，用于随后识别 S100B 和信号输出。AISA 提供了显著积累的电化学活性 Fc 部分，使超灵敏的 S100B 检测低至 0.02 nM，比未放大的方法低 10 倍，优于以前报道的测定方法。作为概念验证研究，进一步的实验还突出了 AISA 的良好重现性和稳定性，并证明了其在模拟血清样本中的可用性。因此，这项工作不仅为超灵敏检测蛋白质生物标志物提供了有价值的检测工具，而且还提倡在电化学生物传感系统中利用聚集诱导信号放大，因为它具有未来实际应用的巨大潜力。
