Singlet oxygen ( 1 O 2 ) has been recently identified as a key molecule against toxic Aβ aggregation, which is associated with the currently incurable Alzheimer's disease (AD). However, limited research has studied its efficiency against tau protein aggregation, the other major hallmark of AD. Herein, we designed and synthesized boron-dipyrromethene (BODIPY)−ruthenium conjugates and isolated three isomers. Under visible-light irradiation, the ε isomer can be photoactivated and efficiently generate singlet oxygen. Particularly, the complex demonstrated successful results in attenuating tauopathy�an appreciable decrease to 43 ± 2% at 100 nM. The photosensitizer was further found to remarkably promote neurite outgrowth and significantly increased the length and number of neurites in nerve cells. As a result of effective photoinduced singlet oxygen generation and proactive neurite outgrowth, the hybrid design has great potential for therapeutics for Alzheimer's disease.
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).
Carbon Monoxide (CO) plays an important role in signaling in the cells, making its use as a therapeutic tool highly intriguing. Reduced burst emissions are important to avoid the cytotoxicity...
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