Nanostars Carrying Multifunctional Neurotrophic Dendrimers Protect Neurons in Preclinical In Vitro Models of Neurodegenerative Disorders
Source abstract
Abstract
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.
Source: openalex_inverted_index · Quality: baseline
Research context
OpenAlex topics: Alzheimer's disease research and treatments · Neuroscience and Neural Engineering · Cholinesterase and Neurodegenerative Diseases
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Materials and London Centre for Nanotechnology, Imperial College, Exhibition Road, LondonSW7 2AZ, UK
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
Centre for Ultrastructural Imaging, Kings College London, LondonSE1 1UL, UK
Department of Chemistry, University College London, 20 Gordon Street, LondonWC1H 0AJ, UK
The Francis Crick Institute, LondonNW11 AT, UK
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
Funding
Engineering and Physical Sciences Research Council · Imperial College London · Medical Research Council · FP7 People: Marie-Curie Actions · Division of Intramural Research, National Institute of Allergy and Infectious Diseases · Royal Society of Chemistry · Michael J. Fox Foundation for Parkinson's Research · Wellcome Trust · Cancer Research UK
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