Toward the Early Evaluation of Therapeutic Effects: An Electrochemical Platform for Ultrasensitive Detection of Apoptotic Cells

Toward the Early Evaluation of Therapeutic Effects: An Electrochemical Platform for Ultrasensitive Detection of Apoptotic Cells
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迈向治疗效果的早期评估:超灵敏检测凋亡细胞的电化学平台

DOI:
10.1021/ac201804b
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发表时间:
2011-10-15
影响因子:
7.4
通讯作者:
Zhu, Jun-Jie
Zhu, Jun-Jie
中科院分区:
化学1区
文献类型:
--
作者:
Zhang, Jing-Jing;Zheng, Ting-Ting;Zhu, Jun-Jie

文献摘要

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早期评估治疗效果的能力是白血病研究中的一个重大挑战。为了应对这一挑战,我们开发了一种新的电化学平台,用于超灵敏和选择性检测对治疗有反应的凋亡细胞。为了构建该平台,首先通过逐层方法将氮掺杂碳纳米管和金纳米颗粒结合在一起后制造了一种新型的三维(3-D)结构。所形成的结构为膜联蛋白V提供了具有高稳定性和生物活性的有效基质,以提高灵敏度。基于膜联蛋白V和凋亡细胞膜上的磷脂酰丝氨酸之间的特异性识别,膜联蛋白V/3-D结构界面显示出捕获凋亡细胞的优越能力。此外,设计了一种基于凝集素的纳米探针的非共价组装的刀豆球蛋白A的CdTe量子点(QDs)标记的二氧化硅纳米球与聚(烯丙胺盐酸盐)作为连接器。该纳米探针结合了特异性碳水化合物识别和基于多标记量子点的信号放大。通过与基于量子点的纳米探针和电化学溶出分析的耦合,所提出的ESTA型细胞传感器表现出优异的分析性能,用于超灵敏检测凋亡细胞(低至48个细胞),揭示了对治疗效果的早期评估的巨大潜力。
The ability for early evaluation of therapeutic effects is a significant challenge in leukemia research. To address this challenge, we developed a novel electrochemical platform for ultrasensitive and selective detection of apoptotic cells in response to therapy. In order to construct the platform, a novel three-dimensional (3-D) architecture was initially fabricated after combining nitrogen-doped carbon nanotubes and gold nanoparticles via a layer-by-layer method. The formed architecture provided an effective matrix for annexin V with high stability and bioactivity to enhance sensitivity. On the basis of the specific recognition between annexin V and phosphatidylserine on the apoptotic cell membrane, the annexin V/3-D architecture interface showed a predominant capability for apoptotic cell capture. Moreover, a lectin-based nanoprobe was designed by noncovalent assembly of concanavalin A on CdTe quantum dots (QDs)-labeled silica nanospheres with poly(allylamine hydrochloride) as a linker. This nanoprobe incorporated both the specific carbohydrate recognition and the multilabeled QDs-based signal amplification. By Coupling With the QD-based nanoprobe and electrochemical stripping analysis, the proposed sandwich-type cytosensor showed an excellent analytical performance for the ultrasensitive detection of apoptotic cells (as low as 48 cells), revealing great potential toward the early evaluation of therapeutic effects.