Nanostars Carrying Multifunctional Neurotrophic Dendrimers Protect Neurons in Preclinical In Vitro Models of Neurodegenerative Disorders.

Autor: Morfill C; Department of Materials and London Centre for Nanotechnology, Imperial College, Exhibition Road, LondonSW7 2AZ, UK., Pankratova S; Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen2200N, Denmark.; Comparative Paediatrics and Nutrition, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen2200N, Denmark., Machado P; Centre for Ultrastructural Imaging, Kings College London, LondonSE1 1UL, UK., Fernando NK; Department of Chemistry, University College London, 20 Gordon Street, LondonWC1H 0AJ, UK., Regoutz A; Department of Chemistry, University College London, 20 Gordon Street, LondonWC1H 0AJ, UK., Talamona F; Department of Materials and London Centre for Nanotechnology, Imperial College, Exhibition Road, LondonSW7 2AZ, UK., Pinna A; Department of Materials and London Centre for Nanotechnology, Imperial College, Exhibition Road, LondonSW7 2AZ, UK.; The Francis Crick Institute, LondonNW11 AT, UK., Klosowski M; Department of Materials and London Centre for Nanotechnology, Imperial College, Exhibition Road, LondonSW7 2AZ, UK., Wilkinson RJ; The Francis Crick Institute, LondonNW11 AT, UK.; Imperial College, Exhibition Road, LondonSW7 2AZ, UK., Fleck RA; Centre for Ultrastructural Imaging, Kings College London, LondonSE1 1UL, UK., Xie F; Department of Materials and London Centre for Nanotechnology, Imperial College, Exhibition Road, LondonSW7 2AZ, UK., Porter AE; Department of Materials and London Centre for Nanotechnology, Imperial College, Exhibition Road, LondonSW7 2AZ, UK., Kiryushko D; Department of Materials and London Centre for Nanotechnology, Imperial College, Exhibition Road, LondonSW7 2AZ, UK.; Centre for Neuroinflammation and Neurodegeneration, Imperial College London, Hammersmith Hospital Campus, Burlington Danes Building, 160 Du Cane Road, LondonW12 0NN, UK.; Experimental Solid State Physics Group, Department of Physics, Imperial College, Exhibition Road, LondonSW72AZ, UK.
Jazyk: angličtina
Zdroj: ACS applied materials & interfaces [ACS Appl Mater Interfaces] 2022 Oct 26; Vol. 14 (42), pp. 47445-47460. Date of Electronic Publication: 2022 Oct 11.
DOI: 10.1021/acsami.2c14220
Abstrakt: A challenge in neurology is the lack of efficient brain-penetrable neuroprotectants targeting multiple disease mechanisms. Plasmonic gold nanostars are promising candidates to deliver standard-of-care drugs inside the brain but have not been trialed as carriers for neuroprotectants. Here, we conjugated custom-made peptide dendrimers (termed H3/H6), encompassing motifs of the neurotrophic S100A4-protein, onto star-shaped and spherical gold nanostructures (H3/H6-AuNS/AuNP) and evaluated their potential as neuroprotectants and interaction with neurons. The H3/H6 nanostructures crossed a model blood-brain barrier, bound to plasma membranes, and induced neuritogenesis with the AuNS, showing higher potency/efficacy than the AuNP. The H3-AuNS/NP protected neurons against oxidative stress, the H3-AuNS being more potent, and against Parkinson's or Alzheimer's disease (PD/AD)-related cytotoxicity. Unconjugated S100A4 motifs also decreased amyloid beta-induced neurodegeneration, introducing S100A4 as a player in AD. Using custom-made dendrimers coupled to star-shaped nanoparticles is a promising route to activate multiple neuroprotective pathways and increase drug potency to treat neurodegenerative disorders.
Databáze: MEDLINE
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