Yan Wang,1,* Cuiying Liu,2,3,* Yanhong Ren,3 Jibin Song,4 Kelong Fan,5 Lizeng Gao,5 Xunming Ji,3 Xiaoyuan Chen,6– 10 Heng Zhao3 

1Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, People’s Republic of China; 2School of Nursing, Capital Medical University, Beijing, People’s Republic of China; 3Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, People’s Republic of China; 4State Key Laboratory of Chemical Resource Engineering, College of Chemistry, Beijing University of Chemical Technology, Beijing, People’s Republic of China; 5CAS Engineering Laboratory for Nanozyme, Institute of Biophysics Chinese Academy of Sciences, Beijing, People’s Republic of China; 6Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore; 7Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 8Nanomedicine Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 9Theranostics Center of Excellence (TCE), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 10Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A*STAR), Singapore

*These authors contributed equally to this work

Correspondence: Heng Zhao; Xiaoyuan Chen, Email hengzhao@ccmu.edu.cn; chen.shawn@nus.edu.sg

Abstract: This review article discusses the potential of nanomaterials in targeted therapy and immunomodulation for stroke-induced immunosuppression. Although nanomaterials have been extensively studied in various biomedical applications, their specific use in studying and addressing immunosuppression after stroke remains limited. Stroke-induced neuroinflammation is characterized by T-cell-mediated immunodepression, which leads to increased morbidity and mortality. Key observations related to immunodepression after stroke, including lymphopenia, T-cell dysfunction, regulatory T-cell imbalance, and cytokine dysregulation, are discussed. Nanomaterials, such as liposomes, micelles, polymeric nanoparticles, and dendrimers, offer advantages in the precise delivery of drugs to T cells, enabling enhanced targeting and controlled release of immunomodulatory agents. These nanomaterials have the potential to modulate T-cell function, promote neuroregeneration, and restore immune responses, providing new avenues for stroke treatment. However, challenges related to biocompatibility, stability, scalability, and clinical translation need to be addressed. Future research efforts should focus on comprehensive studies to validate the efficacy and safety of nanomaterial-based interventions targeting T cells in stroke-induced immunosuppression. Collaborative interdisciplinary approaches are necessary to advance the field and translate these innovative strategies into clinical practice, ultimately improving stroke outcomes and patient care.

Keywords: ischemic stroke, neuroinflammation, T cells, immunosuppression, nanoparticles