H2O2-responsive multifunctional nanocomposite for the inhibition of amyloid-β and Tau aggregation in Alzheimer's disease

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.