Cascade‐Amplified Ratiometric Fluorescent Probe for Time‐Locked Imaging Epilepsy
Abstract
ABSTRACT Accurate localization of the epileptogenic network (EN) is essential for surgical intervention in drug‐resistant epilepsy, which affects over 15 million people globally. However, current approaches are limited by their low specificity, insufficient sensitivity, and challenges in capturing transient epileptiform discharges, which results in surgical success rates ranging from 30% to 70%. Here, we present a cascade‐amplified ratiometric imaging strategy employing an engineered fluorescent polymeric probe (CAR‐FM) that tandemly targets two temporally distinct pathological features within the epileptogenic network: transient acidosis fluctuations triggered by discharges and sustained neuroinflammation. This dual‐cascade amplification enables CAR‐FM to achieve more than a >150‐fold enhancement in fluorescence ratio with markedly improved specificity and sensitivity. In addition, CAR‐FM demonstrates robust applicability across four epilepsy models, which enables time‐locked EN delineation for up to 100 h. In epileptic mouse models, CAR‐FM‐guided resection yields a 67% greater reduction in seizure burden compared to that of conventional electrocorticography. Given its ultrahigh imaging sensitivity and biocompatibility, CAR‐FM offers a clinically translatable strategy for intraoperatively refining EN visualization, which potentially expands the population eligible for epilepsy surgery.
Article Details
Authors (20)
Xin Wang
Bohan Li
Min Li
Yuncan Chen
Department of Neurology, Huashan Hospital Fudan University Shanghai 200040 China
Yurui Tang
Aiyan Ji
State Key Laboratory of Drug Research Molecular Imaging Center Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China
Jing Zhao
Chenchen Sun
Key Laboratory of Material Chemistry for Energy Conversion and Storage Ministry of Education Hubei Key Laboratory of Material Chemistry and Service Failure Hubei Engineering Research Center for Biomaterials and Medical Protective Materials School of Chemistry and Chemical Engineering Huazhong University of Science and Technology Wuhan 430074 P.R. China
Zhenrong Li
School of Pharmacy MOE Key Laboratory of Smart Drug Delivery MOE Innovative Center For New Drug Development of Immune Inflammatory Diseases Department of Pharmacy Zhongshan Hospital Fudan University Shanghai China
Dan Ni
School of Pharmacy MOE Key Laboratory of Smart Drug Delivery MOE Innovative Center For New Drug Development of Immune Inflammatory Diseases Department of Pharmacy Zhongshan Hospital Fudan University Shanghai China
Yanlong Cheng
School of Pharmacy MOE Key Laboratory of Smart Drug Delivery MOE Innovative Center For New Drug Development of Immune Inflammatory Diseases Department of Pharmacy Zhongshan Hospital Fudan University Shanghai China
Wanbing Sun
Department of Neurology and Research Center of Neurology in Second Affiliated Hospital and Key Laboratory of Medical Neurobiology of Zhejiang Province Zhejiang University School of Medicine Hangzhou China
Zuhai Lei
Jing Wang
Hunan Cancer Hospital Changsha China
Annamaria Vezzani
Department of Acute Brain and Cardiovascular Injury Mario Negri Institute for Pharmacological Research IRCCS Milano Italy
Xiaoyu Li
Cong Li
Xiao Zhu
School of Materials Science and Technology
Zhen Cheng
State Key Laboratory of Drug Research, Molecular Imaging Center
Cong Wang
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences & Research Unit of Peptide Science, Chinese Academy of Medical Sciences, 2019RU066