Nanostars Carrying Multifunctional Neurotrophic Dendrimers Protect Neurons in Preclinical In Vitro Models of Neurodegenerative Disorders
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Nanostars Carrying Multifunctional Neurotrophic Dendrimers Protect Neurons in Preclinical In Vitro Models of Neurodegenerative Disorders. / Morfill, Corinne; Pankratova, Stanislava; Machado, Pedro; Fernando, Nathalie K.; Regoutz, Anna; Talamona, Federica; Pinna, Alessandra; Klosowski, Michal; Wilkinson, Robert J.; Fleck, Roland A.; Xie, Fang; Porter, Alexandra E.; Kiryushko, Darya.
In: ACS applied materials & interfaces, Vol. 14, No. 42, 2022, p. 47445–47460.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Nanostars Carrying Multifunctional Neurotrophic Dendrimers Protect Neurons in Preclinical In Vitro Models of Neurodegenerative Disorders
AU - Morfill, Corinne
AU - Pankratova, Stanislava
AU - Machado, Pedro
AU - Fernando, Nathalie K.
AU - Regoutz, Anna
AU - Talamona, Federica
AU - Pinna, Alessandra
AU - Klosowski, Michal
AU - Wilkinson, Robert J.
AU - Fleck, Roland A.
AU - Xie, Fang
AU - Porter, Alexandra E.
AU - Kiryushko, Darya
PY - 2022
Y1 - 2022
N2 - 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
AB - 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
KW - peptides
KW - mimetic
KW - neuron
KW - gold nanostar
KW - neuroprotection
KW - DOPAMINERGIC CELL-DEATH
KW - MTS1 S100A4 PROTEIN
KW - BLOOD-BRAIN-BARRIER
KW - GOLD NANOPARTICLES
KW - OXIDATIVE STRESS
KW - HIPPOCAMPAL-NEURONS
KW - ALZHEIMERS-DISEASE
KW - ERBB4 RECEPTOR
KW - ANIMAL-MODEL
KW - NEUREGULIN-1
U2 - 10.1021/acsami.2c14220
DO - 10.1021/acsami.2c14220
M3 - Journal article
C2 - 36218307
VL - 14
SP - 47445
EP - 47460
JO - ACS applied materials & interfaces
JF - ACS applied materials & interfaces
SN - 1944-8244
IS - 42
ER -
ID: 323201334