Green synthesis of gold nanoparticles using the seaweed Fucus spiralis and their neuroprotective effects in an in vivo zebrafish model of aluminium-induced neurotoxicity

The increasing prevalence of neurodegenerative diseases such as Alzheimer’s disease (AD) underscores the need for effective therapeutic strategies. Nanotechnology can provide new tools to counteract neurotoxicity, namely by improving bioavailability of therapeutic molecules in the brain. Brown seaweeds, such as Fucus spiralis (FS), are rich in bioactive compounds with antioxidant, anti-inflammatory, cytoprotective, and neuroprotective activities, relevant to AD management. Gold nanoparticles (AuNPs) can act as carriers but also display intrinsic antioxidant and anti-inflammatory activities. Its production by green synthesis using biological substrates is attracting attention, as it couples sustainability with enhanced biocompatibility and advantageous bioactivities. In this study, AuNPs were successfully synthesized using Fucus spiralis aqueous extracts (Au@FS). The extracts were biochemically characterized by Fourier-Transform Infrared Spectroscopy and mass spectrometry. The determination of the total phenolic content, ferric reducing ability of plasma and DPPH radical scavenging activity, confirmed high antioxidant potential. The synthesis of Au@FS was confirmed by UV-Vis, and their physico-chemical properties were studied by DLS, ELS, STEM and XRD. The results revealed small (∼ 17 nm wide) and spherical nanoparticles with highly negative surface charge (- 30.5 mV), highlighting their potential to cross the blood-brain barrier. XRD and EDS analysis demonstrated the crystalline and cubic-centered face nature of Au@FS, with ∼ 18 nm diameter. The cytotoxicity profile of the extracts and biosynthesized AuNPs was assessed in human fibroblasts, revealing toxicity only at high concentrations (> 0.60 mg/mL extract). A zebrafish embryo neurotoxicity model was used to evaluate whether FS extracts and derived AuNPs counteracted AD-like symptoms. Au@FS mitigated aluminium chloride-induced developmental delays and cardiotoxicity, enhancing lipid mobilization and ocular development. Moreover, it demonstrated potential to inhibit acetylcholinesterase. These findings highlight a sustainable nanotechnology-based approach integrating marine bioresources and AuNPs, offering a promising strategy for AD management. • Green synthesis of gold nanoparticles using Fucus spiralis (Au@FS) produced small (∼17 nm), spherical, negatively charged nanoparticles with strong antioxidant potential • Fucus spiralis extracts contain antioxidant, anti-inflammatory, cytoprotective and relevant neuroprotective compounds • Extracts and Au@FS showed low cytotoxicity with toxicity only at higher concentrations (>0.60 mg/ml in fibroblasts) • In zebrafish embryos with AD-like neurotoxicity, Au@FS nanoparticles regulated oxidative stress and acetylcholinesterase activity suggesting therapeutic potential against AD hallmarks