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

Autor: Park E; Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College St, Toronto, ON, M5S 3M2, Canada., Li LY; Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College St, Toronto, ON, M5S 3M2, Canada., He C; Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College St, Toronto, ON, M5S 3M2, Canada., Abbasi AZ; Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College St, Toronto, ON, M5S 3M2, Canada., Ahmed T; Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College St, Toronto, ON, M5S 3M2, Canada., Foltz WD; Department of Radiation Oncology, University Health Network, 149 College St, Toronto, ON, M5T 1P5, Canada., O'Flaherty R; Tanz Centre for Research in Neurodegenerative Diseases, Department of Medical Biophysics, University of Toronto, 135 Nassau St, Toronto, ON, M5T 1M8, Canada., Zain M; Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College St, Toronto, ON, M5S 3M2, Canada., Bonin RP; Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College St, Toronto, ON, M5S 3M2, Canada., Rauth AM; Departments of Medical Biophysics and Radiation Oncology, University of Toronto, 101 College St, Toronto, ON, M5G 1L7, Canada., Fraser PE; Tanz Centre for Research in Neurodegenerative Diseases, Department of Medical Biophysics, University of Toronto, 135 Nassau St, Toronto, ON, M5T 1M8, Canada., Henderson JT; Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College St, Toronto, ON, M5S 3M2, Canada., Wu XY; Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College St, Toronto, ON, M5S 3M2, Canada.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2023 Apr; Vol. 10 (12), pp. e2207238. Date of Electronic Publication: 2023 Feb 19.
DOI: 10.1002/advs.202207238
Abstrakt: 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.
(© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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