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

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  • Corinne Morfill
  • Pankratova, Stanislava
  • Pedro Machado
  • Nathalie K. Fernando
  • Anna Regoutz
  • Federica Talamona
  • Alessandra Pinna
  • Michal Klosowski
  • Robert J. Wilkinson
  • Roland A. Fleck
  • Fang Xie
  • Alexandra E. Porter
  • Darya Kiryushko

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 H3AuNS 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

Original languageEnglish
JournalACS applied materials & interfaces
Volume14
Issue number42
Pages (from-to)47445–47460
Number of pages16
ISSN1944-8244
DOIs
Publication statusPublished - 2022

    Research areas

  • peptides, mimetic, neuron, gold nanostar, neuroprotection, DOPAMINERGIC CELL-DEATH, MTS1 S100A4 PROTEIN, BLOOD-BRAIN-BARRIER, GOLD NANOPARTICLES, OXIDATIVE STRESS, HIPPOCAMPAL-NEURONS, ALZHEIMERS-DISEASE, ERBB4 RECEPTOR, ANIMAL-MODEL, NEUREGULIN-1

ID: 323201334