A Biomimetic Upconversion Nanobait-Based Near Infrared Light Guided Photodynamic Therapy Alleviates Alzheimer's Disease by Inhibiting -Amyloid Aggregation

Aberrant beta-amyloid (A beta) fibrillation is the key event in Alzheimer's disease (AD), the inhibition and degradation of which are recognized as a promising therapeutic strategy to alleviate the nerve damage of AD. Photodynamic therapy (PDT) holds great potential for modulation of A beta self-assembly, which is nevertheless limited by the inefficient utilization of reactive oxygen species (ROS). Herein, an erythrocyte membrane (EM)-modified core-shell upconversion nanoparticle (UCNP/Cur@EM) is designed and fabricated as a biomimetic nanobait to improve the PDT efficiency in AD. The UCNP with the outlayer of mesoporous silica is synthesized to load a high amount of the photosensitizer (curcumin), the unique optical feature of which can trigger curcumin to generate ROS upon near-infrared light (NIR) irradiation. Integration of EM enables the biomimetic nanobait to attract A beta peptides trapped in the phospholipid bilayer, restraining the growth of A beta monomers to form aggregates and improving the utilization rate of ROS to degrade the preformed A beta aggregates. In vivo studies demonstrate that UCNP/Cur@EM irradiated by NIR enables to decrease A beta deposits, ameliorates memory deficits, and rescues cognitive functions in the APP/PS1 transgenic mouse model. A biocompatible and controllable way is provided here to inhibit the amyloid protein-associated pathological process of AD.