Photodynamic Alzheimer's disease therapy: From molecular catalysis to photo-nanomedicine

Alzheimer's disease (AD) is a major form of dementia, closely associated with the filamentous assembly of amyloid-β (Aβ) and Tau protein in the brain, which can cause memory and learning deficits. Over the world, developing available AD drugs has been considered as one of the major goals in AD research not only for pharmacology but also for chemistry and biomedicine. However, current strategies to treat AD disease are mainly based on chemotherapy, while very limited AD drugs have been approved by FDA. As an alternative, recently great efforts have been dedicated to employing the photodynamic therapy (PDT) approach to intervene the AD-related protein (e.g., amyloid-β and Tau) aggregations via photon-triggered reactive oxygen species generation. Although photodynamic AD therapy remains in its infancy and many concerns need to be dissolved, it is still believed to serve as a promising alternative to reverse the dilemma of Alzheimer's treatment. With this hope in mind, here we aim to draw a blueprint for this emerging area. In this review, we not only summarize the photochemical principles of AD therapy and the states-of-the-art photodynamic molecules/photo-nanomedicine that are capable of regulating the AD pathological proteins, but also, also the most important, overview the pros and cons of photodynamic AD therapy and give some suggestions for overcoming the challenges in this field. It is our hope that the progress made to date, as summarized in this paper, can inspire future efforts to seek out more promising photochemical approaches, better fitting the clinical requirements of AD therapy.