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

The abnormal accumulation of β-amyloid (Aβ) 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 Aβ 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 Aβ aggregates, we have conjugated the KLVFF peptide which specifically recognizes and captures Aβ 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 β-sheet-rich, long, and entangled Aβ 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 Aβ aggregate-induced neurotoxicity. Our work demonstrates the potential of the KLVFF-Ag:CuBi₂O₄ platform for the targeted disassembly of cytotoxic, robust Aβ aggregates with the aid of NIR energy and cathodic bias.