Nanocarrier-mediated siRNA delivery:a new approach for the treatment of traumatic brain injury-related Alzheimer's disease
Jie Jin
Huajing Zhang
Qianying Lu
Linqiang Tian
Sanqiao Yao
Feng Lai
Yangfan Liang
Chuanchuan Liu
Yujia Lu
Sijia Tian
Yanmei Zhao
Wenjie Ren
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.
Keywords：blood-brain barriercognitive dysfunctionexosomesgene silencingimmunotherapyinorganic nanomaterialsliposome nanoparticlesneuroinflammationpolymer nanoparticlesstem cells
Publication Date：2025-09-27
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：18( 2538-2555 )