Brain‐Penetrating and Disease Site‐Targeting Manganese Dioxide‐Polymer‐Lipid Hybrid Nanoparticles Remodel Microenvironment of Alzheimer's Disease by Regulating Multiple Pathological Pathways
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Brain‐Penetrating and Disease Site‐Targeting Manganese Dioxide‐Polymer‐Lipid Hybrid Nanoparticles Remodel Microenvironment of Alzheimer's Disease by Regulating Multiple Pathological Pathways

Park, Elliya;Li, Lily Yi;He, Chunsheng;Abbasi, Azhar Z.;Ahmed, Taksim;Foltz, Warren D.;O'Flaherty, Regan;Zain, Maham;Bonin, Robert P.;Rauth, Andrew M.;Fraser, Paul E.;Henderson, Jeffrey T.;Wu, Xiao Yu;
advanced science 2023 Vol. 10 pp. n/a-n/a
79
park2023brainpenetratingadvanced

Abstract

Abstract Finding effective disease‐modifying treatment for Alzheimer's disease remains challenging due to an array of factors contributing to the loss of neural function. The current study demonstrates a new strategy, using multitargeted bioactive nanoparticles to modify the brain microenvironment to achieve therapeutic benefits in a well‐characterized mouse model of Alzheimer's disease. The application of brain‐penetrating manganese dioxide nanoparticles significantly reduces hypoxia, neuroinflammation, and oxidative stress; ultimately reducing levels of amyloid β plaques within the neocortex. Analyses of molecular biomarkers and magnetic resonance imaging‐based functional studies indicate that these effects improve microvessel integrity, cerebral blood flow, and cerebral lymphatic clearance of amyloid β. These changes collectively shift the brain microenvironment toward conditions more favorable to continued neural function as demonstrated by improved cognitive function following treatment. Such multimodal disease‐modifying treatment may bridge critical gaps in the therapeutic treatment of neurodegenerative disease.

Keywords

Medicine (General) Engineering (General). Civil engineering (General) Science Diseases of the blood and blood-forming organs agriculture history of scholarship and learning. the humanities social sciences philology. linguistics geology nuclear and particle physics. atomic energy. radioactivity astrophysics stratigraphy

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https://doi.org/10.1002/advs.202207238

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