Key Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, P. R. China.
State Key Laboratory of Bioelectronics, Jiangsu Engineering Laboratory of Smart Carbon-Rich Materials and Device, School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 211189, P. R. China.
Small. 2023 Oct;19(41):e2206959. doi: 10.1002/smll.202206959. Epub 2023 Jun 15.
Excessive accumulations of reactive oxygen species (ROS) and amyloid-β (Aβ) protein are closely associated with the complex pathogenesis of Alzheimer's disease (AD). Therefore, approaches that synergistically exert elimination of ROS and dissociation of Aβ fibrils are effective therapeutic strategies for correcting the AD microenvironment. Herein, a novel near infrared (NIR) responsive Prussian blue-based nanomaterial (PBK NPs) is established with excellent antioxidant activity and photothermal effect. PBK NPs possess similar activities to multiple antioxidant enzymes, including superoxide dismutase, peroxidase, and catalase, which can eliminate massive ROS and relieve oxidative stress. Under the NIR irradiation, PBK NPs can generate local heat to disaggregate Aβ fibrils efficiently. By modifying CKLVFFAED peptide, PBK NPs display obvious targeting ability for blood-brain barrier penetration and Aβ binding. Furthermore, in vivo studies demonstrate that PBK NPs have outstanding ability to decompose Aβ plaques and alleviate neuroinflammation in AD mouse model. Overall, PBK NPs provide evident neuroprotection by reducing ROS levels and regulating Aβ deposition, and may accelerate the development of multifunctional nanomaterials for delaying the progression of AD.
活性氧（ROS）和淀粉样β（Aβ）蛋白的过度积累与阿尔茨海默病（AD）的复杂发病机制密切相关。因此，协同发挥消除 ROS 和解离 Aβ 纤维作用的方法是纠正 AD 微环境的有效治疗策略。本文建立了一种具有优异抗氧化活性和光热效应的新型近红外（NIR）响应普鲁士蓝基纳米材料（PBK NPs）。PBK NPs 具有类似于多种抗氧化酶的活性，包括超氧化物歧化酶、过氧化物酶和过氧化氢酶，可消除大量 ROS 并缓解氧化应激。在 NIR 照射下，PBK NPs 可有效产生局部热量来解聚 Aβ 纤维。通过修饰 CKLVFFAED 肽，PBK NPs 表现出明显的血脑屏障穿透和 Aβ 结合的靶向能力。此外，体内研究表明，PBK NPs 具有出色的分解 Aβ 斑块和减轻 AD 小鼠模型神经炎症的能力。总体而言，PBK NPs 通过降低 ROS 水平和调节 Aβ 沉积来提供明显的神经保护作用，并可能加速用于延缓 AD 进展的多功能纳米材料的发展。
