Polydopamine/Ruthenium Nanoparticle Systems As Photothermal Therapy Reagents and Reactive Oxygen Species Scavengers for Alzheimer’s Disease Treatment

The important causes of microglial dysfunction include continuous accumulation of amyloid beta (Afi) fibrils, elevated reactive oxygen species (ROS), and hypoxia. They may be the key pathogenic mechanism of Alzheimer's disease (AD). Photothermal therapy (PTT) is considered an innovative and noninvasive alternative therapy due to its huge potential, which modulated the decomposition of mature Afi fibrils. Here, we report a polydopamine-ruthenium nanosystem (PDA-Ru) that is simultaneously used as the near-infrared PTT reagent, ROS scavenger, and hydrogen peroxide catalyst. The photothermal conversion performance and catalase activity of PDA were improved by anchoring Ru nanoparticles of small size. In vivo studies demonstrate that PDA-Ru + NIR decreases Afi deposition successfully, thereby restoring the neuroregulatory function of microglia. Ultimately, it ameliorates neuroinflammation and memory deficits in AD mice. In conclusion, the work illustrates that versatile nanomaterial can rescue neuronal damage and modulate microglia. It could serve as a potential strategy for AD treatment and other neurodegenerative diseases.