Nanostars Carrying Multifunctional Neurotrophic Dendrimers Protect Neurons in Preclinical In Vitro Models of Neurodegenerative Disorders
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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 language | English |
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Journal | ACS applied materials & interfaces |
Volume | 14 |
Issue number | 42 |
Pages (from-to) | 47445–47460 |
Number of pages | 16 |
ISSN | 1944-8244 |
DOIs | |
Publication status | Published - 2022 |
- 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
Research areas
ID: 323201334