期刊
ACS APPLIED MATERIALS & INTERFACES
卷 14, 期 42, 页码 47445-47460出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.2c14220
关键词
peptides; mimetic; neuron; gold nanostar; neuroprotection
资金
- European Commission for Research Innovation FP7 [P627049]
- Engineering and Physical Sciences Research Council [EP/L015277/1]
- Doctoral Training Partnership (Engineering and Physical Sciences Research Council)
- Analytical Chemistry Trust Fund
- Francis Crick Institute [FC0010218]
- Cancer Research UK [FC0010218]
- Medical Research Council [FC0010218]
- Meningitis Now
- NIH [R01AI145436]
- Michael J Fox Parkinson's Research Foundation [11713]
- Imperial College London for her Imperial College Research Fellowship
A challenge in neurology is the lack of efficient neuroprotectants that can penetrate the blood-brain barrier and target multiple disease mechanisms. In this study, the authors conjugate custom-made peptide dendrimers with gold nanostructures and demonstrate their potential as neuroprotectants, showing protective effects against oxidative stress and cytotoxicity related to Parkinson's and Alzheimer's disease.
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
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