LAUSR

The abnormal accumulation of β-amyloid (Aβ) aggregates in the brain is a major pathological hallmark of Alzheimer's disease (AD). We report near-infrared (NIR)-active CuBi2O4-based photocathodic platform that can target intact Aβ aggregates and dissociate them into nontoxic species. Due to its relatively narrow bandgap, CuBi2O4 exhibits strong absorption of NIR light, which allows for deeper tissue penetration and less photo-damage of tissues than those of visible light. Furthermore, its high stability in aqueous media, biocompatibility, and robustness against photo-corrosion makes CuBi2O4 an ideal material for medical applications. For 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 with 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 targeted disassembly of cytotoxic, robust Aβ aggregates with the aid of NIR energy and cathodic bias.