A biomimetic upconversion nanoreactors for near-infrared driven H₂ release to inhibit tauopathy in Alzheimer's disease therapy

Abstract

Abnormal hyperphosphorylation of tau protein is a principal pathological hallmark in the onset of neurodegenerative disorders, such as Alzheimer's disease (AD), which can be induced by an excess of reactive oxygen species (ROS). As an antioxidant, hydrogen gas (H<inf>2</inf>) has the potential to mitigate AD by scavenging highly harmful ROS such as •OH. However, conventional administration methods of H<inf>2</inf> face significant challenges in controlling H<inf>2</inf> release on demand and fail to achieve effective accumulation at lesion sites. Herein, we report artificial nanoreactors that mimic natural photosynthesis to realize near-infrared (NIR) light-driven photocatalytic H<inf>2</inf> evolution in situ. The nanoreactors are constructed by biocompatible crosslinked vesicles (CVs) encapsulating ascorbic acid and two photosensitizers, chlorophyll a (Chla) and indoline dye (Ind). In addition, platinum nanoparticles (Pt NPs) serve as photocatalysts and upconversion nanoparticles (UCNP) act as light-harvesting antennas in the nanoreacting system, and both attach to the surface of CVs. Under NIR irradiation, the nanoreactors release H<inf>2</inf> in situ to scavenge local excess ROS and attenuate tau hyperphosphorylation in the AD mice model. Such NIR-triggered nanoreactors provide a proof-of-concept design for the great potential of hydrogen therapy against AD.