biostudies-literatureMorfill CCancer Research UKFP7 People: Marie-Curie ActionsMedical Research CouncilImperial College LondonRoyal Society of ChemistryWellcome TrustDivision of Intramural Research, National Institute of Allergy and Infectious DiseasesEngineering and Physical Sciences Research CouncilMichael J. Fox Foundation for Parkinson's Research47445-47460https://www.ebi.ac.uk/biostudies/studies/S-EPMC9614720biostudies-literatureUnknown14(42)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-ACS applied materials & interfacesNanostars Carrying Multifunctional Neurotrophic Dendrimers Protect Neurons in Preclinical In Vitro Models of Neurodegenerative Disorders.PMC961472011713EP/L015277/1R01AI145436P627049FC0010218Kiryushko DFernando NKPinna APankratova SKlosowski MWilkinson RJMachado PTalamona FMorfill CXie FRegoutz APorter AEFleck RAfalseNanostars Carrying Multifunctional Neurotrophic Dendrimers Protect Neurons in Preclinical In Vitro Models of Neurodegenerative Disorders.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 H3-2022-01-01T00:00:00Z2022 Oct2025-04-04T09:42:22.966Z2025-04-04T09:42:22.966ZS-EPMC96147203621830710.1021/acsami.2c14220