Merocyanine Complexes Coupled with Plasmonic Au Nanoparticles for Inhibiting Tau Aggregation

Singlet oxygen (1O2) has been recently identified as the key mechanism for depressing β-amyloid (Aβ) accumulation and neurofibrillary tangles (NFTs). Slow cell internalization and short half-life of photosensitizing effects still impede the application of nanophotosensitizers for photodynamic therapy (PDT). The current major challenge of using spiropyran for PDT is the extremely short half-life of its ring-opened isomer, merocyanine. Merocyanine is the center of generation of 1O2. Here, we report that the complexation of spiropyran onto Au nanoparticles greatly enhances the stability of merocyanine (half-life is 91.6 h). Additionally, Au nanoparticles sharply decelerate the reversion of merocyanine back to spiropyran (a ring-closed form) by modifying the energy configuration of merocyanine, resulting in generation of a long-lived 1O2 phototherapy response (24 h) in the intracellular environment for depressing tau aggregation (a 32% reduction of NFT formation).