High fidelity detection of miRNAs from complex physiological samples through electrochemical nanosensors empowered by proximity catalysis and magnetic separation

作者全名：Tang, Shuqi; Xie, Xiyue; Li, Lin; Zhou, Luoli; Xing, Yuxin; Chen, Yuhua; Cai, Kaiyong; Li, Fan; Zhang, Jixi

作者地址：[Tang, Shuqi; Xie, Xiyue; Li, Lin; Zhou, Luoli; Xing, Yuxin; Chen, Yuhua; Cai, Kaiyong; Zhang, Jixi] Chongqing Univ, Coll Bioengn, Minist Educ, Key Lab Biorheol Sci & Technol, 174 Shazheng Rd, Chongqing 400044, Peoples R China; [Li, Fan] Chongqing Med Univ, Affiliated Hosp 1, Dept Endocrinol, 1 Youyi Rd, Chongqing 400016, Peoples R China

通信作者：Zhang, JX (通讯作者)，Chongqing Univ, Coll Bioengn, Minist Educ, Key Lab Biorheol Sci & Technol, 174 Shazheng Rd, Chongqing 400044, Peoples R China.; Li, F (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Endocrinol, 1 Youyi Rd, Chongqing 400016, Peoples R China.

来源：BIOSENSORS & BIOELECTRONICS

ESI学科分类：CHEMISTRY

WOS号：WOS:001250358800001

JCR分区：Q1

影响因子：10.7

年份：2024

卷号：260

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Electrochemical detection; Nanosensor; Signal amplification; Proximity catalysis; Interference removal; Tumor markers

摘要：Electrochemical detection of miRNA biomarkers in complex physiological samples holds great promise for accurate evaluation of tumor burden in the perioperative period, yet limited by reproducibility and bias issues. Here, nanosensors installed with hybrid probes that responsively release catalytic DNAzymes (G-quadruplexes/ hemin) were developed to solve the fidelity challenge in an immobilization -free detection. miRNA targets triggered toehold -mediated strand displacement reactions on the sensor surface and resulted in amplified shedding of DNAzymes. Subsequently, the interference background was removed by Fe3O4 core -facilitated magnetic separation. Binding aptamers of the electrochemical reporter (dopamine) were tethered closely to the catalytic units for boosting H2O2-mediated oxidation through proximity catalysis. The one -to -many conversion by dual amplification from biological -chemical catalysis facilitated sufficient homogeneous sensing signals on electrodes. Thereby, the nanosensor exhibited a low detection limit (2.08 fM), and high reproducibility (relative standard deviation of 1.99%). Most importantly, smaller variations (RSD of 0.51-1.04%) of quantified miRNAs were observed for detection from cell lysates, multiplexed detection from unprocessed serum, and successful discrimination of small upregulations in lysates of tumor tissue samples. The nanosensor showed superior diagnostic performance with an area under curve (AUC) of 0.97 and 94% accuracy in classifying breast cancer patients and healthy donors. These findings demonstrated the synergy of signal amplification and interference removal in achieving high-fidelity miRNA detection for practical clinical applications.

基金机构：National Natural Science Foundation of China (NSFC) [22175027, 21734002]; Fundamental Research Funds for the Central Universities [2023CDJXY-051]; Graduate Research and Innovation Foundation of Chongqing [CYS23133]; Natural Science Foundation of Chongqing [cstc2021jcyj-cxttX0002, cstc2021jcyj-msxmX0178]; The 100 Talents Program of Chongqing University

基金资助正文：This work was supported in part by the National Natural Science Foundation of China (NSFC, grant nos. 22175027 and 21734002) , the Fundamental Research Funds for the Central Universities (project no.2023CDJXY-051) , the Graduate Research and Innovation Foundation of Chongqing (Grant no. CYS23133) , the Natural Science Foundation of Chongqing (cstc2021jcyj-cxttX0002 and cstc2021jcyj-msxmX0178) , and the 100 Talents Program of Chongqing University (J.Z.) .