Fluorescence quenching-based immunological probe for ticagrelor monitoring

Shengshuo Zhang; Yueqing Cheng; Yujie Gao; Yujie Zou; Weiling Xiao; Tianyi Li; Mei Li; Bowen Yu; Jinhua Dong

doi:10.3389/fbioe.2023.1295406

Fluorescence quenching-based immunological probe for ticagrelor monitoring

Front Bioeng Biotechnol. 2023 Nov 28:11:1295406. doi: 10.3389/fbioe.2023.1295406. eCollection 2023.

Authors

Shengshuo Zhang^{1

2}, Yueqing Cheng¹, Yujie Gao¹, Yujie Zou¹, Weiling Xiao³, Tianyi Li⁴, Mei Li¹, Bowen Yu³, Jinhua Dong^{2

5}

Affiliations

¹ School of Life Science and Technology, Weifang Medical University, Weifang, China.
² School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao, China.
³ School of Basic Medical Sciences, Weifang Medical University, Weifang, China.
⁴ School of Stomatology, Weifang Medical University, Weifang, China.
⁵ International Research Frontiers Initiative, Tokyo Institute of Technology, Yokohama, Japan.

Abstract

Introduction: Ticagrelor is extensively utilized for the treatment of acute coronary syndromes (ACS), but its platelet aggregation inhibitory effects can potentially result in tissue bleeding, posing a serious risk to patients' lives. Methods: In this study, we developed highly sensitive full length anti-ticagrelor Quenchbodies (Q-bodies) for fast monitoring of ticagrelor both in solution and serum for the first time. Ticagrelor coupled with N- hydroxysuccinimide (Ticagrelor-NHS) ester was also designed and synthesized for interaction and biological activity detection. Results: Both ATTO-labeled MEDI2452 (2452A) Q-body and TAMRA-labeled IgG 152 (152T) Q-body demonstrated efficient detection of ticagrelor and its active metabolite (TAM). The 2452A Q-body exhibited a broader detection range, while the 152T Q-body displayed a lower limit of detection (LOD). Under physiological conditions (Ticagrelor:TAM, 3:1), the concentration of ticagrelor was further measured, yielding LOD values of 4.65 pg/mL and 2.75 pg/mL for the two Q-bodies, with half-maximal effect concentrations of 8.15 ng/mL and 3.0 ng/mL, respectively. Discussion: Compared with traditional liquid chromatography-mass spectrometry (LC-MS) methods, anti-ticagrelor Q-bodies have higher sensitivity and detection speed. It enabled the completion of analysis within 3 min, facilitating rapid preoperative detection of blood drug concentration in ACS to determine the feasibility of surgery and mitigate the risk of intraoperative and postoperative hemorrhage. The swift detection of ticagrelor holds promise for enhancing individualized drug administration, preventing adverse reactions, and providing preoperative guidance.

Keywords: Q-body; acute coronary syndrome; full-length IgG; immunofluorescence sensor; rapid detection; ticagrelor.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was partly funded by the Shandong Provincial Natural Science Foundation, China (Grant Number: ZR2022QC209) and the Weifang Medical University Domestic Visiting Scholar Project. This work was also partly funded by the World Research Hub (WRH) Program of the International Research Frontiers Initiative, Tokyo Institute of Technology.