H_(2)O_(2)-responsive multifunctional nanocomposite for the inhibition of amyloid-βand Tau aggregation in Alzheimer's disease

Amyloid-β(Aβ)and Tau proteins are the main components of Aβplaques and neurofibrillary tangles in Alzheimer's disease(AD),and their abnormal ag-gregation is closely related to the pathogenesis of AD.The production of reactive oxygen species(ROS)and the aggregation of Aβand Tau form a vi-cious circle,which leads to the aggravation of AD.However,inhibiting the aggregation of Aβand Tau or scavenging ROS is not able to effectively reverse the progression of AD.Herein,we prepared a H_(2)O_(2) responsive multifunctional nanocomposite UCNPs@mSiO_(2)-MB@AuNPs(abbreviated as USMA)to inhibit the aggregation of Aβand Tau.In this system,USMA could respond to H_(2)O_(2) to detach gold nanoparticles(AuNPs)and lead to the release of meth-ylene blue(MB)from mesoporous silica(mSiO_(2)),where AuNPs and MB can inhibit Aβand Tau aggregation,respectively.Furthermore,USMA could consume H_(2)O_(2) by reacting with them.Meanwhile,upconversion lumines-cence 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.Impor-tantly,the USMA can effectively reduce the cytotoxicity induced by Aβand Tau aggregation.This work opens up a possibility to improve therapeutic ef-ficacy for the treatment of AD.