Near-Infrared-Active Copper Bismuth Oxide Electrodes for Targeted Dissociation of Alzheimer's β-Amyloid Aggregates

The abnormal accumulation of beta-amyloid (A beta) aggregates in the brain is a major pathological hallmark of Alzheimer's disease. We report a near-infrared (NIR)-active CuBi2O4-based photocathodic platform that can target intact A beta aggregates and dissociate them into nontoxic species. Because of its relatively narrow band gap, CuBi2O4 exhibits strong absorption of NIR light, which allows for deeper tissue penetration and causes less photodamage to tissues compared to visible light. Furthermore, its high stability in aqueous media, biocompatibility, and robustness against photocorrosion make CuBi2O4 an ideal material for medical applications. For the targeted clearance of A beta aggregates, we have conjugated the KLVFF peptide which specifically recognizes and captures A beta aggregates on the surface of silver-doped CuBi2O4 (Ag:CuBi2O4). Upon illumination of NIR light under a cathodic bias, the KLVFF-immobilized Ag:CuBi2O4 (KLVFF-Ag:CuBi2O4) effectively dissociated beta-sheet-rich, long, and entangled A beta fibrillary aggregates into small fragmented, soluble species through photo-oxygenation. We also verified that the KLVFF-Ag:CuBi2O4 photocathode is biocompatible and effective in reducing A beta aggregate-induced neurotoxicity. Our work demonstrates the potential of the KLVFF-Ag:CuBi2O4 platform for the targeted disassembly of cytotoxic, robust A beta aggregates with the aid of NIR energy and cathodic bias.