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基于血红素/G-四链体 DNA zyme 和 PdRu/Pt 异质结构的电化学生物传感器作为信号放大器用于循环肿瘤细胞检测。

An electrochemical biosensor based on hemin/G-quadruplex DNAzyme and PdRu/Pt heterostructures as signal amplifier for circulating tumor cells detection.

机构信息

Key Laboratory of Clinical Laboratory Diagnostics (Chinese Ministry of Education), College of Laboratory Medicine, Chongqing Medical Laboratory Microfluidics and SPRi Engineering Research Center, Chongqing Medical University, No. 1 Yi Xue Yuan Road, Chongqing 400016, PR China.

Clinical Laboratory Medicine Center, Chongqing University Cancer Hospital, Chongqing 400030, PR China.

出版信息

J Colloid Interface Sci. 2021 Oct;599:752-761. doi: 10.1016/j.jcis.2021.05.006. Epub 2021 May 5.

DOI:10.1016/j.jcis.2021.05.006
PMID:33989928
Abstract

Metastasis due to circulating tumor cells (CTCs) shed from the original tumor accounts for the majority of cancer-related death. Efficient CTCs detection is pivotal to the diagnosis of early cancer metastasis. In this work, Platinum nanoparticles (PtNPs) decorated hyperbranched PdRu nanospines (PdRu/Pt) hierarchical structures were firstly synthesized to detect CTCs with the assistance of DNAzyme. Meanwhile, Super P and gold nanoparticles (AuNPs) acted as sensing medium to improve electrical conductivity and immobilization of anti-EpCAM antibody to specifically capture model CTCs. After immune-conjugation of anti-EpCAM-MCF-7-signal probes on the gold electrode, PtNPs, PdRu nanospines (PdRuNSs) and hemin/G-quadruplex co-catalyzed substrate HO to realize multiplexed signal amplification, which significantly improves the analytical performance of the electrochemical biosensor. As-proposed biosensor reached a limit of detection (LOD) down to 2 cells mL and showed a wide detection range of 2 to 10 cells mL. Application of the biosensor to detect MCF-7 cells spiked human blood samples further demonstrated the feasibility for early cancer evaluation in clinic.

摘要

由于源自原始肿瘤的循环肿瘤细胞 (CTC) 脱落而导致的转移是大多数癌症相关死亡的原因。有效的 CTC 检测对于癌症转移的早期诊断至关重要。在这项工作中,首先合成了铂纳米粒子 (PtNPs) 修饰的支化 PdRu 纳米刺 (PdRu/Pt) 分级结构,以在 DNAzyme 的辅助下检测 CTC。同时,Super P 和金纳米粒子 (AuNPs) 用作传感介质,以提高电导率并固定抗 EpCAM 抗体,从而特异性捕获模型 CTC。在金电极上免疫共轭抗 EpCAM-MCF-7-信号探针后,PtNPs、PdRu 纳米刺 (PdRuNSs) 和血红素/G-四链体共催化底物 HO 实现了多重信号放大,显著提高了电化学生物传感器的分析性能。所提出的生物传感器的检测限 (LOD) 低至 2 个细胞 mL,检测范围为 2 到 10 个细胞 mL。该生物传感器在检测 MCF-7 细胞掺杂人血样本中的应用进一步证明了其在临床早期癌症评估中的可行性。

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