Photoresponsive materials for intensified modulation of Alzheimer's amyloid-β protein aggregation: A review

Abstract

The abnormal self-assembly of amyloid-β protein (Aβ) into toxic aggregates is a major pathological hallmark of Alzheimer's disease (AD). Modulation of Aβ fibrillization with pharmacological modalities has become an active field of research, which aims to mitigate Aβ-induced neurotoxicity and ameliorate impaired recognition. Among the various strategies for AD treatment, phototherapy, including photothermal therapy (PTT), photodynamic therapy (PDT), and photoresponsive release systems have attracted increased attention because of the spatiotemporal controllability. Under the irradiation of light, the heat or reactive oxygen species generated by photothermal or photodynamic processes significantly enhances the efficacy of the inhibitor or modulator, and the “caged” drug can be accurately released at the intended site, thus avoiding adverse effects. This review, from a viewpoint of materials, focuses on the recent advances in modulating Aβ aggregation by light that irradiates on the materials that function on modulating Aβ aggregation. Representative examples of PTT, PDT, and photoresponsive drug release systems are discussed in terms of inhibitory mechanism, the unique properties of materials, and the design of modulators. The major challenges of phototherapy against AD are addressed and the promising prospects are proposed. It is concluded that the noninvasive light-assisted approaches will become a promising strategy for intensifying the modulation of Aβ aggregation and thus facilitating AD treatment. Statement of significanceAlzheimer's disease (AD) with the hallmark of amyloid-β protein (Aβ) deposition is affecting more than 50 million people globally. It is urgent to explore intelligent materials to modulate Aβ aggregation. This review summarizes the intensified modulation of Aβ aggregation by a variety of photoresponsive materials including photothermal, photosensitizing and photoresponsive release materials, focusing on their characteristics and functionalities. We believe this review would arouse more interest in the research field of stimuli-responsive materials and promote their clinical applications in AD therapy.