Mesoporous silica-coated gold nanorods functionalized with the D3 peptide and loaded with epigallocatechin-3-gallate reduce β-amyloid toxicity in the presence of Zn(II) ions.

Alzheimer's disease (AD) is characterized, among other factors, by the accumulation of the β-amyloid peptide (Aβ), redox imbalance, and disruption of metal homeostasis-processes that act synergistically, promoting neurotoxicity. In this work, a core-shell nanosystem based on mesoporous silica-coated gold nanorods (GNR@mSiO2) was developed, functionalized with the anti-Aβ aggregation D3 peptide and loaded with epigallocatechin-3-gallate (EGCG), an antioxidant and modulator of Aβ aggregation and toxicity, to reduce Aβ-induced toxicity in vitro in presence of Zn(II) ions. Nanosystem formation and the incorporation of each component were confirmed by transmission electron microscopy (TEM), UV-Vis-NIR spectroscopy, dynamic light scattering (DLS), ζ-potential, and fourier transform infrared (FT-IR) spectroscopy. The GNR@mSiO2-PEG-D3/EGCG nanosystem exhibited high antioxidant activity, evidenced by its ability to sequester metal ions and deactivate DPPH• and •OH radicals. Furthermore, it effectively inhibited Aβ aggregation and promoted its disaggregation, particularly under Zn(II) ions overload conditions. In differentiated SH-SY5Y neuronal cells, the nanosystem converted Aβ aggregates formed in the presence of Zn(II) ions into non-toxic species, resulting in a marked reduction of cytotoxicity and intracellular ROS production. Taken together, these findings highlight the potential of GNR@mSiO2-PEG-D3/EGCG as a promising multifunctional platform against AD.