Neural Regeneration Research ›› 2025, Vol. 20 ›› Issue (9): 2538-2555.doi: 10.4103/NRR.NRR-D-24-00303

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Nanocarrier-mediated siRNA delivery: a new approach for the treatment of traumatic brain injury–related Alzheimer’s disease

Jie Jin1, #, Huajing Zhang1, 2, #, Qianying Lu1, 2, #, Linqiang Tian3, 4, Sanqiao Yao5, 6, Feng Lai3 , Yangfan Liang1 , Chuanchuan Liu1 , Yujia Lu1 , Sijia Tian1 , Yanmei Zhao1, 2, *, Wenjie Ren3, 4, 5, *   

  1. 1 Institute of Disaster and Emergency Medicine, Tianjin University, Tianjin, China;  2 Key Laboratory for Disaster Medicine Technology, Tianjin, China;  3 Henan Medical Key Laboratory for Research of Trauma and Orthopedics, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan Province, China;  4 Clinical Medical Center of Tissue Engineering and Regeneration, Xinxiang Medical University, Xinxiang, Henan Province, China;  5 Institutes of Health Central Plain, Xinxiang Medical University, Xinxiang, Henan Province, China;  6 School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province, China
  • Online:2025-09-15 Published:2024-12-28
  • Contact: Yanmei Zhao, PhD, zhaoyanmei@tju.edu.cn; Wenjie Ren, PhD, xxmu_rwj@163.com.
  • Supported by:
    This work was supported by Open Project of the Key Laboratory of Trauma and Orthopedics Research Medicine in Henan Province, No. HZKFKT20220504 (to YZ); the National Natural Science Foundation of China, No. 32000877 (to YZ); and Open Scientific Research Program of Military Logistics, No. BLB20J009 (to YZ).

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Abstract: Traumatic brain injury and Alzheimer’s disease share pathological similarities, including neuronal loss, amyloid-β deposition, tau hyperphosphorylation, blood–brain barrier dysfunction, neuroinflammation, and cognitive deficits. Furthermore, traumatic brain injury can exacerbate Alzheimer’s disease-like pathologies, potentially leading to the development of Alzheimer’s disease. Nanocarriers offer a potential solution by facilitating the delivery of small interfering RNAs across the blood–brain barrier for the targeted silencing of key pathological genes implicated in traumatic brain injury and Alzheimer’s disease. Unlike traditional approaches to neuroregeneration, this is a molecular-targeted strategy, thus avoiding non-specific drug actions. This review focuses on the use of nanocarrier systems for the efficient and precise delivery of siRNAs, discussing the advantages, challenges, and future directions. In principle, siRNAs have the potential to target all genes and non-targetable proteins, holding significant promise for treating various diseases. Among the various therapeutic approaches currently available for neurological diseases, siRNA gene silencing can precisely “turn off” the expression of any gene at the genetic level, thus radically inhibiting disease progression; however, a significant challenge lies in delivering siRNAs across the blood–brain barrier. Nanoparticles have received increasing attention as an innovative drug delivery tool for the treatment of brain diseases. They are considered a potential therapeutic strategy with the advantages of being able to cross the blood–brain barrier, targeted drug delivery, enhanced drug stability, and multifunctional therapy. The use of nanoparticles to deliver specific modified siRNAs to the injured brain is gradually being recognized as a feasible and effective approach. Although this strategy is still in the preclinical exploration stage, it is expected to achieve clinical translation in the future, creating a new field of molecular targeted therapy and precision medicine for the treatment of Alzheimer’s disease associated with traumatic brain injury.

Key words: blood–brain barrier,  cognitive dysfunction,  exosomes,  gene silencing,   immunotherapy,  inorganic nanomaterials,  liposome nanoparticles,   neuroinflammation,   polymer nanoparticles,  stem cells