Biotechnologie et biomatériaux

Abstrait

Newly Designed Magnetic and Non-Magnetic Nanoparticles for Potential Diagnostics and Therapy of Alzheimer's Disease

Hadas Skaat and Shlomo Margel

The pathogenesis of many neurodegenerative diseases, including Alzheimer’s disease (AD) is characterized by protein aggregation into amyloid fibrils. In AD, the fibrils are of the amyloid-β (Aβ) peptide. The development of new approaches based on nanotechnology for early detection and potential treatment of AD is of high current interest. This review describes a pioneering approach involving the design, synthesis and utilization of new engineered magnetic and non-magnetic nanoparticles for inhibition and acceleration of conformational changes of the fibrilforming proteins, e.g. insulin and amyloid-β 40 (Aβ40) proteins. A novel method for detection of the location and removal of precursor protofibrils and fibrils by their selective marking by functional magnetic iron oxide nanoparticles was also demonstrated. These non-fluorescent and fluorescent iron oxide (maghemite, γ-Fe2O3) nanoparticles of narrow size distribution were synthesized by controlled nucleation and growth mechanism. Surface coatings of these nanoparticles with a functional fluorinated polymer and peptides, e.g. Leu-Pro-Phe-Phe-Asp (LPFFD) and Aβ40, through various activation methods, were performed. New uniform biocompatible α-amino acid-based polymer nanoparticles containing hydrophobic dipeptides in the polymer side chains were also synthesized. The effect of these nanoparticles on amyloid fibril formation kinetics was elucidated. These engineered nanoparticles are effective in the study and control of the process of amyloid fibril formation, and as selective biomarkers of amyloid plaques for multimodal imaging. This study may contribute to the mechanistic understanding of the protein aggregation processes, leading to development of new diagnostic and therapeutic strategies against amyloid-related diseases.