Near-Infrared-Active Copper Bismuth Oxide Electrodes for Targeted Dissociation of Alzheimer's β-Amyloid Aggregates.,ACS Applied Materials & Interfaces

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Near-Infrared-Active Copper Bismuth Oxide Electrodes for Targeted Dissociation of Alzheimer's β-Amyloid Aggregates.
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2020-05-04 , DOI: 10.1021/acsami.0c02349
Yerin Heo ₁ , Kayoung Kim ₁ , Jinhyun Kim ₁ , Jinhyeong Jang ₁ , Chan Beum Park ₁

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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.

中文翻译：

用于阿尔茨海默氏症β-淀粉样蛋白聚集体靶向解离的近红外活性铜铋氧化物电极。

β-淀粉样蛋白（Aβ）聚集在大脑中的异常积累是阿尔茨海默氏病的主要病理标志。我们报告了一个基于近红外（NIR）的基于CuBi2O4的光阴极平台，该平台可以靶向完整的Aβ聚集体并将其解离为无毒物种。由于其相对较窄的带隙，CuBi2O4表现出对NIR光的强吸收性，与可见光相比，它能使组织穿透更深，对组织的光损伤更少。此外，CuBi2O4在水性介质中的高稳定性，生物相容性和对光腐蚀的耐受性使其成为医疗应用的理想材料。为了有针对性地清除Aβ聚集体，我们共轭了KLVFF肽，该肽可特异性识别并捕获掺银CuBi2O4（Ag：CuBi2O4）表面上的Aβ聚集体。在阴极偏压下照射NIR光后，固定KLVFF的Ag：CuBi2O4（KLVFF-Ag：CuBi2O4）通过光氧合有效地将富含β-折叠的，长且缠结的Aβ纤维状聚集体分解成小的碎片，可溶物质。我们还验证了KLVFF-Ag：CuBi2O4光电阴极具有生物相容性，可有效减少Aβ聚集体诱导的神经毒性。我们的工作证明了KLVFF-Ag：CuBi2O4平台借助NIR能量和阴极偏压可有针对性地分解具有细胞毒性的强大Aβ聚集体。CuBi2O4光电阴极具有生物相容性，可有效降低Aβ聚集体诱导的神经毒性。我们的工作证明了KLVFF-Ag：CuBi2O4平台借助NIR能量和阴极偏压可有针对性地分解具有细胞毒性的强大Aβ聚集体。CuBi2O4光电阴极具有生物相容性，可有效降低Aβ聚集体诱导的神经毒性。我们的工作证明了KLVFF-Ag：CuBi2O4平台借助NIR能量和阴极偏压可有针对性地分解具有细胞毒性的强健Aβ聚集体的潜力。

更新日期：2020-05-04

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