Amyloid fishing: Functionalized Titania nanoparticles for amyloid fibril targeting and inhibition

Amyloidoses are a family of diseases characterized by abnormal protein folding that leads to aggregation. Amyloid proteins accumulate to form fibrils and plaques which are implicated in the pathogenesis of Alzheimer, prion, diabetes type II and other diseases. Despite extensive research efforts devoted to plaque aggregates inhibition, there is yet no cure for this phenomenon.

In recent years there has been growing interest in utilizing titanium and its alloys in biomedical applications. Various surface modification that produce porous, adhesive, bioactive coatings have been developed. Titanium oxides (titania) are also being developed for photothermal and photodynamic treatments.

Inspired by our recent studies on peptide coated titanium surfaces [1], we set to explore the effect of functionalized titania nanoparticles as potential agents against amyloids. Titania nanoparticles were coated with bi-functional catechol derivatives (dihydroxy-phenylalanine propanoic acid, denoted DPA) to gain targeting properties. Titania modified 5 nm nanoparticles, coated with DPA were further conjugated to the amyloid-targeting Congo Red (CR) dye. Titania-DPA-CR nanoparticles were found to target mature amyloid fibril of both amyloid-b (Ab 1-42 a.a) and prion peptide (PrP fragment, 106-126 a.a). Moreover, amyloids fibrillation in presence of the modified nanoparticles decreased dramatically. This work provides new insights into the use of modified titania nanoparticles for amyloid plaque targeting and inhibition. It may shed light on future modifications and functionalization of nanoparticles for different applications.

References

1. Gitelman, A. & Rapaport, H. Bifunctional Designed Peptides Induce Mineralization and Binding to TiO₂. Langmuir 30, 47164724 (2014).