Photoelectrochemical dissociation of β-Amyloid Aggregates by $CuBi_2O_4$ photocathode

Abstract

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 $CuBi_2O_4$-based photocathodic platform that can target intact Aβ aggregates and dissociate them into nontoxic species. Because of its relatively narrow band gap, $CuBi_2O_4$ exhibits 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 $CuBi_2O_4$ 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 $CuBi_2O_4$ ($Ag:CuBi_2O_4$). Upon illumination of NIR light under a cathodic bias, the KLVFF-immobilized $Ag:CuBi_2O_4$ (KLVFF-$Ag:CuBi_2O_4$) 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-$Ag:CuBi_2O_4$ photocathode is biocompatible and effective in reducing Aβ aggregate-induced neurotoxicity. Our work demonstrates the potential of the KLVFF$Ag:CuBi_2O_4$ platform for the targeted disassembly of cytotoxic, robust Aβ aggregates with the aid of NIR energy and cathodic bias.