期刊
ACS APPLIED MATERIALS & INTERFACES
卷 15, 期 46, 页码 53177-53188出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.3c08756
关键词
Alzheimer's disease; lesion-recognizing nanoparticles; small interfering RNA; intranasal administration; mesenchymal stem cell-derived exosomes
Gene therapy has great potential in treating neurodegenerative diseases with complex pathologies. In this study, lesion-recognizing nanoparticles were constructed for the synergistic treatment of Alzheimer's disease. These nanoparticles can cross the nasal mucosa and migrate to the affected brain areas, reducing inflammation and achieving targeted drug release. The lesion-recognizing nanoparticles have shown significant therapeutic effects in the experiments.
Gene therapy has great potential in treating neurodegenerative diseases with complex pathologies. The combination of small interfering RNAs (siRNAs) targeting beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) and caspase-3 will provide an effective treatment option for Alzheimer's disease (AD). To overcome the multiple physiological barriers and improve the therapeutic efficacy of siRNAs, lesion-recognizing nanoparticles (NPs) are constructed in this study for the synergistic treatment of AD. The lesion-recognizing NPs contain rabies virus glycoprotein peptide-modified mesenchymal stem cell-derived exosomes as the shell and a reactive oxygen species (ROS)-responsive polymer loaded with siRNAs as the core. After intranasal administration, the lesion-recognizing NPs cross the nasal mucosa and migrate to the affected brain areas. Furthermore, the NPs recognize the target cells and fuse with the cell membranes of neurons. The cores of NPs directly enter into the cytoplasm and achieve the controlled release of siRNAs in a high-ROS environment to downregulate the level of BACE1 and caspase-3 to ameliorate neurologic injury. In addition, lesion-recognizing NPs can significantly reduce the number of reactive astrocytes. Lesion-recognizing NPs have a positive effect on regulating the phase of neurons and astrocytes, which results in better restoration of memory deficits in 3 x Tg-AD mice. Therefore, this work provides a promising platform for neurodegenerative disease treatment.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据