Exploring Bimetallic Nanoparticles in Alzheimer's Therapy: A Novel Bio-Assisted Synthesis with Multitarget Potential.

Area of Science:

• Nanotechnology and Materials Science
• Biomedical Engineering
• Neuroscience

Background:

• Metal nanoparticles (NPs), particularly gold (AuNPs) and silver (AgNPs), show potential for treating neurodegenerative diseases like Alzheimer's.
• Bimetallic Au/Ag-NPs offer synergistic potential but face limitations in synthesis, biocompatibility, and versatility due to traditional methods.
• Bio-based synthesis presents an innovative solution to overcome these limitations and enhance NP therapeutic efficacy.

Purpose of the Study:

• To develop a novel bio-based synthesis of bimetallic Au/Ag-NPs using collagen-mimicking peptide nanofibers.
• To evaluate the efficacy of these green bimetallic NPs in inhibiting amyloid-beta (Aβ) aggregation.
• To assess the multi-targeted therapeutic potential of Au/Ag-NPs against Alzheimer's disease hallmarks, including esterase inhibition and reactive oxygen species (ROS) reduction.

Main Methods:

• Synthesis of bimetallic gold/silver nanoparticles (Au/Ag-NPs) utilizing collagen-mimicking peptide nanofibers as a bioactive template.
• Assessment of Aβ protein aggregation inhibition compared to individual AuNPs and AgNPs.
• Evaluation of inhibitory activity against esterase and reactive oxygen species (ROS).

Main Results:

• The synthesized green Au/Ag-NPs demonstrated significant inhibition of Aβ aggregation (74%), outperforming individual AuNPs (66%) and AgNPs (43%).
• Bimetallic Au/Ag-NPs exhibited notable inhibitory activity against esterase (∼50%) and ROS (∼75%).
• Au/Ag-NPs showed enhanced cellular barrier penetration, 3D uptake, and endosomal escape capabilities.

Conclusions:

• Bio-synthesized bimetallic Au/Ag-NPs using peptide nanofibers represent a promising multi-targeted therapeutic strategy for Alzheimer's disease.
• These NPs offer mechanistic benefits including Aβ and acetylcholinesterase (AChE) inhibition, ROS reduction, and improved cellular internalization.
• This research advances the development of novel treatments for neurodegenerative disorders, moving beyond the focus on monometallic nanoparticles.