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Publication Detail
Nanostars Carrying Multifunctional Neurotrophic Dendrimers Protect Neurons in Preclinical In Vitro Models of Neurodegenerative Disorders
  • Publication Type:
    Journal article
  • Authors:
    Morfill C, Pankratova S, Machado P, Fernando NK, Regoutz A, Talamona F, Pinna A, Klosowski M, Wilkinson RJ, Fleck RA, Xie F, Porter AE, Kiryushko D
  • Publisher:
    American Chemical Society (ACS)
  • Publication date:
  • Pagination:
    47445, 47460
  • Journal:
    ACS Applied Materials and Interfaces
  • Volume:
  • Issue:
  • Medium:
  • Status:
  • Country:
    United States
  • Language:
  • Keywords:
    S100A4, gold nanostar, mimetic, neuron, neuroprotection, peptides
  • Notes:
    This is an open access article issued under a Creative Commons CC BY licence. For further information, see https://pubs.acs.org/page/rightslinkno.jsp
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.
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