Search

Abstract Amyloid‐β (Aβ) and Tau proteins are the main components of Aβ plaques and neurofibrillary tangles in Alzheimer's disease (AD), and their abnormal aggregation is closely related to the pathogenesis of AD. The production of reactive oxygen species (ROS) and the aggregation of Aβ and Tau form a vicious circle, which leads to the aggravation of AD. However, inhibiting the aggregation of Aβ and Tau or scavenging ROS is not able to effectively reverse the progression of AD. Herein, we prepared a H2O2 responsive multifunctional nanocomposite UCNPs@mSiO2‐MB@AuNPs (abbreviated as USMA) to inhibit the aggregation of Aβ and Tau. In this system, USMA could respond to H2O2 to detach gold nanoparticles (AuNPs) and lead to the release of methylene blue (MB) from mesoporous silica (mSiO2), where AuNPs and MB can inhibit Aβ and Tau aggregation, respectively. Furthermore, USMA could consume H2O2 by reacting with them. Meanwhile, upconversion luminescence of UCNPs can be used to track USMA and monitor MB release, which could provide information on the content of MB in the lesion area. Importantly, the USMA can effectively reduce the cytotoxicity induced by Aβ and Tau aggregation. This work opens up a possibility to improve therapeutic efficacy for the treatment of AD.

The development of nanosystems, which can photooxygenate amyloid-β (Aβ), detect the Tau protein, and inhibit effectively the Tau aggregation, is increasingly important in the diagnosis and therapy of Alzheimer’s disease (AD). Herein, UCNPs-LMB/VQIVYK (UCNPs: upconversion nanoparticles, LMB: Leucomethylene blue, and VQIVYK: Biocompatible peptide) is designed as a HOCl-controlled released nanosystem for AD synergistic treatment. Under exposure to high levels of HOCl, the released MB from UCNPs-LMB/VQIVYK will produce singlet oxygen (1O2) under red light to depolymerize Aβ aggregation and reduce cytotoxicity. Meanwhile, UCNPs-LMB/VQIVYK can act as an inhibitor to decrease Tau-induced neurotoxicity. Besides, UCNPs-LMB/VQIVYK can be used for upconversion luminescence (UCL) due to its unexceptionable luminescence properties. This HOCl-responsive nanosystem offers a new therapy for AD treatment.