2023
DOI: 10.1021/acsami.3c08756
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Enhanced Nose-to-Brain Delivery of Combined Small Interfering RNAs Using Lesion-Recognizing Nanoparticles for the Synergistic Therapy of Alzheimer’s Disease

Jiaxin Li,
Huan Peng,
Wen Zhang
et al.

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 lesi… Show more

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Cited by 11 publications
(4 citation statements)
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“…Additionally, MSC-derived EVs decreased reactive astrocyte numbers. Collectively, these strategies synergistically ameliorated AD pathologies and cognitive deficits 149 .…”
Section: Engineered Sc-evs For Therapiesmentioning
confidence: 95%
See 1 more Smart Citation
“…Additionally, MSC-derived EVs decreased reactive astrocyte numbers. Collectively, these strategies synergistically ameliorated AD pathologies and cognitive deficits 149 .…”
Section: Engineered Sc-evs For Therapiesmentioning
confidence: 95%
“…Such studies in larger animals provide data that are more closely aligned with the pharmacokinetic profiles observed in humans, offering valuable and relevant information for translational research. Additionally, efforts in biotechnology are necessary to prolong the residence time of drugs within the nasal cavity, thereby increasing bioavailability 149 , 150 . Integrating EVs into formulations such as hydrogels could extend mucus retention and enhance bioavailability.…”
Section: Route Of Administrationmentioning
confidence: 99%
“…This research reached a pivotal milestone in demonstrating the therapeutic potential of this exosome-mediated siRNA delivery strategy by achieving a significant knockdown of both mRNA (60%) and protein (62%) levels of BACE1, which is a crucial target implicated in AD in wild-type mice. 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 ]. They further complexed therapeutic siRNAs with a ROS-responsive polymer, cationic polymer poly-[(2-methacryloyl)ethyl(p-boronic acid benzyl) dimethylammonium bromide] (BA-PDMAEMA, BAP), to ensure release in the ROS-rich environment of AD-affected neurons.…”
Section: Applications Of Evs As Nanotheranostic Targets In Cnsmentioning
confidence: 99%
“…Time spent by mice in the target quadrant (Bottom left), Number of times the mice crossed the hidden platform (Bottom right). Reproduced with permission from [ 242 ]. Copyright © 2023, American Chemical Society, and (B) Schematic diagram of the gold nanoparticle-labeled exosome neuroimaging in AD (Top), and longitudinal homing and accumulation of MSC-exo in diseased brains (Bottom).…”
Section: Applications Of Evs As Nanotheranostic Targets In Cnsmentioning
confidence: 99%