Enhanced Photodynamic Therapy for Neurodegenerative Diseases: Development of Azobenzene‐Spiropyran@Gold Nanoparticles for Controlled Singlet Oxygen Generation

The development of durable photosensitizers is pivotal for advancing phototherapeutic applications in biomedicine. Here, we introduce a core-shell azobenzene-spiropyran structure on gold nanoparticles, engineered to enhance singlet oxygen generation. These nano-photosensitizers exhibit increased structural stability and thermal resistance, as demonstrated by slowed O-N-C bond recombination dynamics via in-situ Raman spectroscopy. Notably, the in-situ formation of merocyanine and a light-induced compact shell arrangement extend its half-life from 47 minutes to over 154 hours, significantly boosting singlet oxygen output. The nano-photosensitizer also shows high biocompatibility and notably inhibits tau protein aggregation in neural cells, even with phosphatase inhibitors. Further, it promotes dendritic growth in neuro cells, doubling typical lengths. This work not only advances chemical nanotechnology but also sets a foundation for developing long-lasting phototherapy agents for treating neurodegenerative diseases.