Photothermal nano-agents: an innovative trident weapon for accurate and effective treatment of alzheimer’s disease

Alzheimer's disease (AD) is a degenerative neurological illness for which effective therapy alternatives are currently lacking. Photothermal therapy (PTT) employs the localized thermal effects of nano-photothermal agents (NPTAs) under near-infrared (NIR) light for the treatment of diverse conditions. PTT presents numerous benefits for AD therapy, including operational flexibility, non-invasiveness, spatiotemporal modulation, and synergistic multimodal treatment approaches. The primary mechanisms of PTT for AD treatment encompass the following facets: Initially, localized heat impacts may transiently disrupt the blood-brain barrier (BBB), facilitating the trans-BBB transport of therapeutic medicines. Secondly, the photothermal action can efficiently dissociate Aβ aggregates and Tau protein while inhibiting Aβ aggregation, hence diminishing neurotoxicity and reinstating cognitive function. Third, during PTT, NPTAs can achieve imaging of biomarkers such as Aβ and Tau at the site of AD lesions and actively monitor the therapy process. Despite being in its nascent stages for AD treatment and encountering numerous challenges, such as poor biocompatibility, inadequate penetration of deep brain tissue by NIR light, and cumulative toxicity risks, PTT remains a promising therapeutic strategy to overcome the limitations of AD treatment. This study elucidates the pathophysiology of AD, the processes by which NPTAs enter the brain, and the mechanism of NPTAs in AD theranostics, with a particular focus on current developments in NIR-activated NPTAs for AD treatment. It further discusses the challenges in this emerging field and proposes future research directions, thereby facilitating the clinical translation of PTT-based strategies in AD treatment.