Light‐Induced Chiral Iron Copper Selenide Nanoparticles Prevent β‐Amyloidopathy In Vivo

Abstract

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‐FexCuySe 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‐FexCuySe NPs have a much higher affinity for Aβ42 fibrils than l‐FexCuySe NPs and chiral Cu2−xSe NPs. The chiral FexCuySe NPs also generate more reactive oxygen species (ROS) than chiral Cu2−xSe 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‐FexCuySe 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.

The Coppery Age: Copper (Cu)‐Involved Nanotheranostics

“…Based on the in vivo 4T1 tumor-bearing female BALB/c mice model, the Reproduced with permission. [95] Copyright 2020, Wiley-VCH.…”

“…Based on this fact, chiral l / d ‐Fe x Cu y Se nanoparticles (abbreviated as l / d ‐NPs) were engineering for responding to 808 nm laser irradiation and producing ROS (single oxygen and hydroxyl radicals) without photothermal effect, which converted the dense structure of A β 42 fibrils into looser monomers ( Figure a). [ 95 ] Especially, the d ‐Fe x Cu y Se nanoparticles exhibited an enhanced affinity for A β 42 fibrils as compared to either l ‐Fe x Cu y Se or chiral Cu 2− x Se nanoparticles. Based on the injection of d ‐Fe x Cu y Se nanoparticles into the brains of APP/PS1 transgenic mouse model followed by NIR irradiation each day in 60 days (Figure 6b), the in vivo experiment signified that they significantly decreased the A β 42 concentration in the AD mice within two months (Figure 6c).…”

“…10 Fe x Cu y Se Photothermal therapy Protecting the A 42-induced neuronal damage and mitigating the symptoms in AD mouse model. [95] 11…”

<p>Innovative Therapies and Nanomedicine Applications for the Treatment of Alzheimer’s Disease: A State-of-the-Art (2017–2020)</p>

“…Furthermore, these data were confirmed in vivo; indeed, D-Fe x Cu y Se NPs removed amyloid plaques with a concomitant significant recovery of the cognitive abilities of AD mice. 59 The application of some NPs led to the observation of other potential benefits, probably related to the anti-Aβ activities. Indeed, the chronic treatment of AD mice with redox NPs reduced Aβ plaques, increased antioxidant enzymatic activity, and ameliorated cognitive deficits.…”

“…60 PLGA NPs functionalized with a vitamin D-binding protein showed not only in vitro inhibition of Aβ aggregation, but also reduction of neuroinflammation, neuronal loss, and cognitive dysfunction in AD mice. 61 However, the disruption of Aβ aggregates is sometimes mediated by ROS generation, 57,59 therefore, for these nanodevices, the eventual worsening of AD neuronal damages and neuroinflammation due to an increased oxidative stress seems mandatory to be tested.…”