Nanostars carrying multifunctional neurotrophic dendrimers protect neurons in preclinical in vitro models of neurodegenerative disorders
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2022-10-26
Date Acceptance
2022-09-26
Citation
ACS Applied Materials and Interfaces, 2022, 14 (42), pp.47445-47460
ISSN
1944-8244
Publisher
American Chemical Society
Start Page
47445
End Page
47460
Journal / Book Title
ACS Applied Materials and Interfaces
Volume
14
Issue
42
Copyright Statement
Copyright © 2022 The Authors. Published by American Chemical Society. This publication is licensed under
CC-BY 4.0.
CC-BY 4.0.
License URL
Identifier
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000869075300001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
Subjects
ALZHEIMERS-DISEASE
ANIMAL-MODEL
BRAIN
DOPAMINERGIC CELL-DEATH
ERBB4 RECEPTOR
GOLD NANOPARTICLES
gold nanostar
HIPPOCAMPAL-NEURONS
Materials Science
Materials Science, Multidisciplinary
mimetic
MTS1 S100A4 PROTEIN
Nanoscience & Nanotechnology
NEUREGULIN-1
neuron
neuroprotection
OXIDATIVE STRESS
peptides
Science & Technology
Science & Technology - Other Topics
Technology
Publication Status
Published
Date Publish Online
2022-10-11