Gold nanoparticles incorporating rutin hydrate for targeting oxidative stress-driven neurodegeneration

Neurodegenerative disorders (NDs), exemplified by Alzheimer's disease (AD), present a global health challenge driven by oxidative stress, with current therapies hampered by poor blood-brain barrier (BBB) permeability. In this study, green-synthesized rutin hydrate (RH)-capped metallic gold nanoparticles (RH-AuNPs) were developed and, for the first time, evaluated for stability, biocompatibility, and antioxidant potential in SH-SY5Y cells under oxidative stress, compared to conventional gold NPs (AuNPs) and free RH. Nanoparticles (NPs) were characterized using UV-Visible spectroscopy, dynamic light scattering for particle size and distribution and surface charge, Fourier transform infrared spectroscopy (FTIR) and scanning transmission electron microscopy (STEM). Their in chemico antioxidant potential was assessed via DPPH assay, while in vitro biocompatibility was evaluated using WST-1, and cellular antioxidant activity was determined using both plate-based DCF assay, fluorescence DCF microscopy, and MitoSOX microscopy to assess intracellular and mitochondrial ROS. The RH-AuNPs exhibited favourable physicochemical traits (λmax = 523 nm, size = 34.043 ± 0.041 nm, polydispersity index (PDI) = 0.391 ± 0.003, and zetapotential (ZP) = -30.23 ± 0.569 mV) and robust biocompatibility (> 80% cell viability). Their antioxidant activity matched established antioxidants and significantly surpassed conventional AuNPs. Critically, in vitro studies demonstrated RH-AuNPs' potent antioxidant radical scavenging, outperforming both AuNPs and the RH, thereby inferring their neuroprotective capabilities. RH-AuNPs represent a promising green-synthesized neurotherapeutic platform that combines antioxidant potency, biocompatibility, and ideal characteristics, which would enable downstream potential for effective BBB penetration and neuronal protection against oxidative stress.