Enhanced Nose-to-Brain Delivery of Combined Small Interfering RNAs Using Lesion-Recognizing Nanoparticles for the Synergistic Therapy of Alzheimer’s Disease
Abstract
Gene therapy has great potential in treating neurodegenerative diseases with complex pathologies. The combination of small interfering RNAs (siRNAs) targeting β-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 × Tg-AD mice. Therefore, this work provides a promising platform for neurodegenerative disease treatment.
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Li et al. modified MSC-derived exosomes with RVG peptide (REXO), which binds specifically to neuronal acetylcholine receptors.
“Recently, Li et al. advanced targeted drug delivery by modifying MSC-derived exosomes (MSC-exo) with RVG peptide with 29 amino acids (REXO), which binds specifically to neuronal acetylcholine receptors [242].”
From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [242]
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- Authors
- Li, J., Peng, H., Zhang, W., Li, M., Wang, N., Peng, C., Zhang, X., & Li, Y.
- Affiliations
- University of Science and Technology Beijing (CN)
- Tsinghua University (CN)
- Beijing Key Laboratory for Bioengineering and Sensing Technology, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China
- Corresponding author
- Li, Yan
- Venue
- ACS Applied Materials & Interfaces
- Publisher
- American Chemical Society (ACS)
- Published
- 2023-11-08
- Volume
- 15
- Issue
- 46
- Pages
- 53177-53188
- ISSN
- 1944-8244 (ISSN-L)
- 1944-8252
- OpenAlex
- W4388484583
- Cited by
- 43
- References
- 52
- Citations by year
- 2026: 11 · 2025: 20 · 2024: 11 · 2023: 1
- FWCI
- 3.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- ACS Applied Materials & Interfaces (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fundamental Research Funds for the Central Universities (06500230)
- National Natural Science Foundation of China (32071391)
- Beijing Nova Program (20230484423, Z201100006820140)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Alzheimer's disease, nose-to-brain delivery, siRNA delivery, BACE1, caspase-3, rabies virus glycoprotein, mesenchymal stem cell-derived exosomes, intranasal administration, neurodegeneration, reactive astrocytes, memory impairment
- MeSH terms
- Alzheimer Disease, Animals, Brain, Amyloid beta-Peptides, Aspartic Acid Endopeptidases, Reactive Oxygen Species, Neurodegenerative Diseases, RNA, Small Interfering, Mice, Caspase 3, Nanoparticles, Amyloid Precursor Protein Secretases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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