State Key Lab of Food Science and Technology, International Joint Research Laboratory for Biointerface and Biodetection, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, 214122, P. R. China.
Angew Chem Int Ed Engl. 2020 Apr 27;59(18):7131-7138. doi: 10.1002/anie.202002028. Epub 2020 Mar 10.
The accumulation and deposition of β-amyloid (Aβ) plaques in the brain is considered a potential pathogenic mechanism underlying Alzheimer's disease (AD). Chiral l/d-Fe Cu Se nanoparticles (NPs) were fabricated that interfer with the self-assembly of Aβ42 monomers and trigger the Aβ42 fibrils in dense structures to become looser monomers under 808 nm near-infrared (NIR) illumination. d-Fe Cu Se NPs have a much higher affinity for Aβ42 fibrils than l-Fe Cu Se NPs and chiral Cu Se NPs. The chiral Fe Cu Se NPs also generate more reactive oxygen species (ROS) than chiral Cu Se NPs under NIR-light irradiation. In living MN9D cells, d-NPs attenuate the adhesion of Aβ42 to membranes and neuron loss after NIR treatment within 10 min without the photothermal effect. In-vivo experiments showed that d-Fe Cu Se NPs provide an efficient protection against neuronal damage induced by the deposition of Aβ42 and alleviate symptoms in a mouse model of AD, leading to the recovery of cognitive competence.
β-淀粉样蛋白(Aβ)斑块在大脑中的积累和沉积被认为是阿尔茨海默病(AD)潜在的致病机制。合成了手性 l/d-Fe Cu Se 纳米颗粒(NPs),它们可以干扰 Aβ42 单体的自组装,并在 808nm 近红外(NIR)光照下促使 Aβ42 原纤维变成更松散的单体。d-Fe Cu Se NPs 与 l-Fe Cu Se NPs 和手性 Cu Se NPs 相比,对 Aβ42 原纤维具有更高的亲和力。在手性 Fe Cu Se NPs 下,NIR 光照射后产生的活性氧(ROS)比手性 Cu Se NPs 更多。在活的 MN9D 细胞中,d-NPs 在 10min 内减轻了 Aβ42 与细胞膜的黏附以及 NIR 处理后的神经元损失,而没有光热效应。体内实验表明,d-Fe Cu Se NPs 能有效防止 Aβ42 沉积引起的神经元损伤,并缓解 AD 小鼠模型的症状,从而恢复认知能力。