2. Academic Validation
  3. Ultrabright ratiometric Raman-guided epilepsy surgery by intraoperatively visualizing proinflammatory microglia

Ultrabright ratiometric Raman-guided epilepsy surgery by intraoperatively visualizing proinflammatory microglia

  • Cell Rep Med. 2025 Jun 17;6(6):102155. doi: 10.1016/j.xcrm.2025.102155.
Cong Wang 1,  Zhi Li 2,  Xiao Zhu 3,  Wanbing Sun 4,  Yue Ding 5,  Wenjia Duan 6,  Difei Wang 7,  Yiqing Jiang 8,  Ming Chen 9,  Yuncan Chen 10,  Jiayi Hu 8,  Zheping Cai 11,  Jing Zhao 8,  Junfeng Wang 8,  Zhen Fan 9,  Faming Zheng 12,  Xingyu Zhou 13,  Fang Xie 14,  Jianping Zhang 15,  Yihui Guan 14,  Kui Yan 16,  Zuhai Lei 8,  Qinyue Wang 10,  Luting Wang 17,  Xiao Xiao 18,  Hairong Zheng 19,  Liang Chen 20,  Cong Li 21,  Ying Mao 22
Affiliations

Affiliations

  • 1 MOE Key Laboratory of Smart Drug Delivery, MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases, School of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, China; Greater Bay Area Institute of Precision Medicine (Guangzhou), Fudan University, Guangzhou, China; The Key Laboratory of Biomedical Imaging Science and System, Chinese Academy of Sciences, State Key Laboratory of Biomedical Imaging Science and System, Shenzhen 518055, China. Electronic address: cong_wang@fudan.edu.cn.
  • 2 Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China; Department of Neurosurgery/Neuro-oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
  • 3 Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fudan University, Shanghai, China.
  • 4 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.
  • 5 Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 6 Academy of Forensic Science, Shanghai Key Laboratory of Forensic Medicine (21DZ2270800), Shanghai Key Laboratory of Forensic Medicine, Key Laboratory of Forensic Science, Ministry of Justice, 200063 Shanghai, China.
  • 7 Department of Neurosurgery, Kings College Hospital NHS Foundation Trust, Denmark Hill, London, UK.
  • 8 MOE Key Laboratory of Smart Drug Delivery, MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases, School of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, China.
  • 9 Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
  • 10 Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
  • 11 Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Ministry of Education, Behavioral and Cognitive Neuroscience Center, Institute of Science and Technology for Brain-Inspired Intelligence, Shanghai, China; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai, China.
  • 12 State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, China.
  • 13 Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
  • 14 PET Center, Huashan Hospital, Fudan University, Shanghai, China.
  • 15 Shanghai Engineering Research Center for Molecular Imaging Probes, Shanghai, China.
  • 16 Department of Chemistry, State Key Laboratory of Molecular Engineering of Polymers, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials and iChem, Fudan University, Shanghai, China.
  • 17 Shanghai Institute of Materia Medica Chinese Academy of Sciences, Shanghai, China.
  • 18 Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Ministry of Education, Behavioral and Cognitive Neuroscience Center, Institute of Science and Technology for Brain-Inspired Intelligence, Shanghai, China; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai, China. Electronic address: xiaoxiao@fudan.edu.cn.
  • 19 Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China. Electronic address: hr.zheng@siat.ac.cn.
  • 20 Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai, China; Shanghai Key Lab of Brain Function Restoration and Neural Regeneration, Shanghai, China; Tianqiao and Chrissy Chen Institute for Translational Research, Shanghai, China. Electronic address: hschenliang@fudan.edu.cn.
  • 21 MOE Key Laboratory of Smart Drug Delivery, MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases, School of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, China; The Key Laboratory of Biomedical Imaging Science and System, Chinese Academy of Sciences, State Key Laboratory of Biomedical Imaging Science and System, Shenzhen 518055, China; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai, China. Electronic address: congli@fudan.edu.cn.
  • 22 Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai, China; Shanghai Key Lab of Brain Function Restoration and Neural Regeneration, Shanghai, China. Electronic address: maoying@fudan.edu.cn.
PMID: 40449482 DOI: 10.1016/j.xcrm.2025.102155
Abstract

Resective surgery is an effective approach for long-term seizure control in drug-resistant focal epilepsy when the epileptic focus (EF) can be accurately delineated and removed. However, intraoperative mapping of EF with electrocorticography is laborious, time-consuming, and highly vulnerable to the effects of anesthesia. Here, we demonstrated that activated microglia can be reliable biomarkers for EF localization. Leveraging a newly developed ratiometric Raman nanosensor, ultraHOCls, we successfully visualize proinflammatory microglia in live epileptic mice, allowing for precise EF delineation without the interference of anesthesia. Compared to electrocorticography-guided surgery, ultraHOCl-guided surgery results in a substantial 61% reduction in total seizure burden in epileptic mouse models. Notably, ultraHOCls sprayed on freshly excised human brain tissues can effectively discriminate epileptic regions from non-epileptic tissues with high sensitivity (94.89%) and specificity (93.3%). This work provides an alternative strategy for delineating the EF intraoperatively, potentially revolutionizing surgery outcomes in epilepsy patients.

Keywords

HOCl; Raman imaging; electrocorticography; epilepsy; microglia; myeloperoxidase; ratiometric; surgery.

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