Multifunctional fluorescence sensor as a potential theranostic agent against Alzheimer's disease

Metal ions play an important role in the pathogenesis of Alzheimer's disease (AD). Metal dyshomeostasis, β-amyloid (Aβ) accumulation and oxidative stress, etc. are related to metal ions. So, metal therapeutics has aroused increasingly more attention, especially the research of metal-involved theranostic agents. In this work, a highly selective and sensitive multifunctional fluorescence sensor 1 with a naphthol unit based on photoinduced electron transfer (PET) and excited state proton transfer (ESPT) mechanism was synthesized, and its synergistic biological effects on regulating metal dyshomeostasis, modulating Aβ accumulation and scavenging reactive oxygen species (ROS) was evaluated. The results demonstrated that 1 exhibited significant fluorescence enhancement towards Al³⁺ (the limit was as low as 0.01 ppm), superior chelating abilities with metal ions, even better modulation effect of Cu²⁺-induced Aβ_1-42 accumulation than curcumin, good elimination effect of ROS, clear fluorescence image in living cells, low cytotoxic and appropriate blood brain barrier (BBB) permeability. Overall, these findings revealed that 1 could be used as a potential theranostic agent against AD for further research.