Computationally Guided Protein-Gold Nanostructures for Targeted Recognition and Cleavage of Human Amyloid-β Plaques

Here we report a computationally guided protein-gold hybrid nanostructure, Aβ3FTnAu, which integrates Aβ-recognition motifs into self-assembled human ferritin nanocages containing confined gold nanostructures, enabling selective engagement and disassembly of aggregated human Aβ. Structural analysis and molecular simulations reveal that the engineered nanostructure establishes multivalent interactions with fibrillar Aβ and perturbs key stabilizing interfaces, leading to progressive fibril destabilization.

In 5×FAD transgenic mice, systemic administration of Aβ3FTnAu reduced cerebral amyloid burden, preserved synaptic integrity, and improved cognitive performance. This work establishes a rationally designed bioactive nanomaterial for targeted remodeling of pathological protein aggregates and highlights a generalizable strategy for engineering functional nanostructures to intervene in neurodegenerative proteinopathies.