301. Biofilm-camouflaged Prussian blue synergistic mitochondrial mass enhancement for Alzheimer's disease based on Cu 2+ chelation and photothermal therapy.
- Author
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Li L, Xiong Y, Zhang Y, Yan Y, Zhao R, Yang F, and Xie M
- Subjects
- Animals, Reactive Oxygen Species metabolism, Mice, Transgenic, Mice, Humans, Male, Blood-Brain Barrier metabolism, Erythrocytes drug effects, Ferrocyanides chemistry, Alzheimer Disease drug therapy, Alzheimer Disease therapy, Copper chemistry, Copper administration & dosage, Mitochondria drug effects, Mitochondria metabolism, Photothermal Therapy methods, Amyloid beta-Peptides metabolism, Biofilms drug effects, Chelating Agents chemistry, Nanoparticles
- Abstract
Alzheimer's disease (AD) is one of the most common neurodegenerative diseases characterized by cognitive and memory impairment. Metal ion imbalance and Mitochondrial dysfunction, leading to abnormal aggregation of β-amyloid protein (Aβ), are key factors in the pathogenesis of AD. Therefore, we designed a composite nanometer system of red blood cell (RBC) membranes-encapsulated Prussian blue nanoparticles (PB/RBC). Prussian blue nanoparticles (PBNPs) can chelate Cu
2+ and reduce reactive oxygen species (ROS). The RBC membranes are a kind of natural long-lasting circulating carrier. At the same time, through NIR irradiation, the excellent photothermal ability of PBNPs can also temporarily open the blood-brain barrier (BBB), enhance the transmission efficiency of PB/RBC across the BBB, and depolymerize the formed Aβ deposits, thereby achieving the optimal therapeutic effect. In vitro and in vivo studies demonstrated that PB/RBC could inhibit Cu2+ -induced Aβ monomers aggregation, eliminate the deposition of Aβ plaques, improve the quality of mitochondria, restore the phagocytic function of microglia, alleviate neuroinflammation in APP/PS1 mice, and repair memory damage. In conclusion, our biofilm-camouflaged nano-delivery system provides significant neuroprotection by inhibiting Cu2+ -induced Aβ monomers aggregation, photothermally depolymerizing Aβ fibrils and reducing the level of ROS, thus effectively ameliorating and treating AD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)- Published
- 2024
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