2. Academic Validation
  3. Intranasal delivery of engineered extracellular vesicles promotes neurofunctional recovery in traumatic brain injury

Intranasal delivery of engineered extracellular vesicles promotes neurofunctional recovery in traumatic brain injury

  • J Nanobiotechnology. 2025 Mar 21;23(1):229. doi: 10.1186/s12951-025-03181-9.
Pengtao Li # 1,  Sishuai Sun # 1,  Xingyu Zhu 2,  Xiaoyu Liu 1,  Rui Yin 1,  Yihao Chen 1,  Jianbo Chang 1,  Liguo Ye 1,  Jingxi Gao 2,  Xiaoyan Zhao 2,  Houshi Xu 1,  Yue Wang 1,  Wei Zuo 1,  Zhao Sun 3,  Shihua Wang 2,  Xiao Zhang 1,  Junji Wei 4,  Robert Chunhua Zhao 5,  Qin Han 6
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
  • 2 School of Basic Medicine, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
  • 3 Department of Oncology, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
  • 4 Department of Neurosurgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China. weijunji@pumch.cn.
  • 5 School of Basic Medicine, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China. zhaochunhua@ibms.pumc.edu.cn.
  • 6 School of Basic Medicine, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China. hangin@ibms.pumc.edu.cn.
  • # Contributed equally.
PMID: 40114197 DOI: 10.1186/s12951-025-03181-9
Abstract

Traumatic brain injury (TBI) is a leading cause of disability in adults, significantly affecting patients' quality of life. Extracellular vesicles (EVs) derived from human adipose-derived mesenchymal stem cells (hADSCs) have demonstrated therapeutic potential in TBI treatment. However, their limited targeting ability, short half-life, and low bioavailability present significant challenges for clinical application. In this study, we engineered extracellular vesicles (EEVs) by transfecting hADSCs with lentivirus and incorporating ultra-small paramagnetic nanoparticles (USPNs), resulting in EVs with enhanced miRNA expression and targeted delivery capabilities. These EEVs were administered intranasally to specifically target injury sites, effectively modulating the NF-κB signaling pathway to suppress neuroinflammation. In both in vitro and in vivo assessments, EEVs exhibited superior efficacy in promoting neurofunctional recovery and neurogenesis after brain injury compared to unmodified EVs. Furthermore, validation using human brain Organoid models confirmed EEVs' remarkable ability to suppress neuroinflammation, offering a promising strategy for TBI treatment.

Keywords

Engineered extracellular vesicles; NF-κB; Neurofunctional recovery; Neuroinflammation; Traumatic brain injury.

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