Memory and mood-enhancing neuroprotective effects of visible light photoactivated gold nanoparticles and PEG3350 coating in a rat animal model.

Gold nanoparticles (AuNPs) emerge as promising neuromodulatory biomaterials due to their tunable optical properties, biocompatibility, and ability to cross the blood-brain barrier. Here, we investigated the behavioral and neuroprotective effects of citrate-stabilized AuNPs (~ 19 nm) coated with PEG3350 and irradiated under white (AuWL+PEG) or green light (AuGL+PEG), compared with non-irradiated PEGylated AuNPs (AuNP+PEG). Comprehensive physicochemical analyses demonstrated that green-light irradiation enhanced surface plasmon resonance (SPR) activity, improved PEG adsorption, and yielded superior colloidal stability relative to white-light irradiation. In vivo evaluation in Wistar rats revealed that AuGL+PEG produced robust anxiolytic-like effects in the elevated plus maze, significantly enhanced spatial working memory in the Y-maze, and improved performance in the radial arm maze, approaching the efficacy of donepezil. In the forced swimming test, AuGL+PEG also produced the most favorable antidepressant-like profile, reducing immobility without locomotor confounds. Biochemically, AuGL+PEG markedly enhanced antioxidant capacity, increasing SOD, CAT, GPX, and GSH levels while reducing lipid peroxidation (MDA), consistent with restored redox homeostasis. Acetylcholinesterase inhibition was significantly greater in irradiated groups, supporting improved cholinergic signaling. Toxicological evaluation indicated no major systemic or hematological toxicity at the administered doses. Collectively, the findings demonstrate that light-engineered PEGylated AuNPs, particularly those activated with green light, exhibit potent neuroprotective and cognition-enhancing effects mediated by plasmonic surface optimization, antioxidant defense reinforcement, and cholinergic modulation. These results identify AuGL+PEG as a promising candidate nanomaterial for future applications in neuromodulation, cognitive enhancement, and the treatment of neurodegenerative diseases.