Metal-involved theranostics: An emerging strategy for fighting Alzheimer's disease

Alzheimer's disease (AD) is the most prevalent illness among the neurodegenerative disorders that are progressive, irreversible and incurable so far. Although the etiological mechanism of AD is still not fully understood, considerable evidences support the idea that metals are critically involved as factors or cofactors in the etiopathogenesis of the disease. As a result, metal-involved hypotheses, such as the amyloid cascade hypothesis, the metal ion hypothesis and the oxidative stress hypothesis, are prevailing in the etiology of AD, leading to the development of metal-involved therapeutics. However, current approaches treat patients after first diagnosis using separate therapeutic and diagnostic agents, which is unfavorable for exploring the optimal therapeutic time window and efficacy of the drugs. Theranostics that combines therapy and diagnosis into a single package can efficiently exert the synergistic effect of individual drugs. Thus, as a cutting-edge tool, metal-involved theranostics has promising potential to overcome the weakness of traditional approaches to AD therapy. This review focuses on the reported metal-involved theranostic agents based on metal chelators, metal complexes, and metal nanoparticles. Their design principles, mechanism of action and potential applications are elaborated in detail. The limits and potential directions of this emerging strategy are also discussed with a view to future research.