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Updated: Jan 11, 2026
Fabrication of Amyloid-β-Secreting Alginate Microbeads for Use in Modelling Alzheimer's Disease
Published on: July 6, 2019
Mesenchymal stem cell-derived nanovesicles coated PLGA nanoparticle (MSC-PLGA-NPs) remodel lysosomal function to
Yuankai Gu1,2, Mengqi Hao2,3, Li Wang1,2
1Department of Neurology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Aims:
To develop a novel multifunctional nanoparticle platform by combining mesenchymal stem cell-derived nanovesicles (MSC-NVs) with poly(lactic-coglycolic acid) (PLGA) nanoparticles for Alzheimer's disease (AD) therapy.
Materials & Methods:
Mesenchymal stem cell-derived nanovesicle-poly(lactic-coglycolic acid) nanoparticles (MSC-PLGA-NPs) were prepared via sonication-loading. Blood-brain barrier (BBB) penetration was evaluated using in vitro transwell models and in vivo mouse models. Lysosomal function, autophagy, pathological protein clearance, and anti-inflammatory effects were assessed using various cellular and molecular biology techniques.
Results:
MSC-PLGA-NPs demonstrated 2.3-fold higher BBB penetration efficiency compared to PLGA alone. In a chloroquine(CQ)-induced lysosomal injury model and mice model, they effectively restored lysosomal pH, enhanced autophagy (reducing LC3-II/I ratio by 0.4-fold and p62 expression by 52%), cleared amyloid precursor protein (APP) and phosphorylated tau (p-tau) proteins, and inhibited IL-6 and TNF-α without hepatorenal toxicity.
Conclusions:
These results demonstrate that MSC-PLGA-NPs, a novel multifunctional nanoparticle platform, synergistically integrates the BBB penetration capability of MSC-NVs and the lysosomal acidification function of PLGA. The synergistic combination represents a pioneering "delivery-repair-clearance" integrated strategy for AD therapy. Offering significant advantages over single-component approaches, MSC-PLGA-NPs provide a promising preclinical candidate and new insight into lysosome-targeted nanomedicines for neurodegenerative diseases.
