Garofalide_2026_Pharmaceutics_18_

Background: In this work, gold nanoparticles synthesized by the chemical method were exposed to natural green light, then associated with a lipid layer of phosphatidylcholine by physical adsorption, without excluding their partial encapsulation. Methods: A suspension of lipid vesicles grafted with irradiated nanoparticles (Au(ir)L) was obtained that showed improved colloidal stability, evidenced by a higher negative potential (-23.8 mV compared to -17.08 mV for AuL), an increased hydrodynamic size, and a higher lipid coverage, suggesting improved nanoparticle-membrane electrostatic interactions. The biological effects of these vesicles were evaluated in a zebrafish model of scopolamine-induced cognitive impairment. Behavioral and biochemical analyses were conducted to assess their impact on anxiety-like behavior, memory, and oxidative stress, using galantamine as a reference compound. Results: Under non-induced conditions, no significant behavioral differences were observed between the control and nanoparticle-treated groups, supporting the biocompatibility of the formulations. In scopolamine-treated zebrafish, both AuL and Au(ir)L showed partial improvements in behavioral parameters; however, these effects were not consistently statistically significant across all endpoints. Notably, more consistent effects were observed at the biochemical level, where both formulations, particularly Au(ir)L, significantly modulated acetylcholinesterase activity and reduced markers of oxidative stress, including lipid peroxidation. Conclusions: Overall, these findings suggest that lipid-grafted gold nanoparticles, especially in their irradiated form, exhibit moderate neuroprotective potential, primarily supported by biochemical outcomes and accompanied by partial behavioral improvements.