CeO₂ In Situ Growth on Red Blood Cell Membranes: CQD Coating and Multipathway Alzheimer’s Disease Therapy under NIR

Abstract

Alzheimer's disease (AD) has a complex etiology and diverse pathological processes. The therapeutic effect of single-target drugs is limited, so simultaneous intervention of multiple targets is gradually becoming a new research trend. Critical stages in AD progression involve amyloid-β (Aβ) self-aggregation, metal-ion-triggered fibril formation, and elevated reactive oxygen species (ROS). Herein, red blood cell membranes (RBC) are used as templates for the in situ growth of cerium oxide (CeO₂) nanocrystals. Then, carbon quantum dots (CQDs) are encapsulated to form nanocomposites (CQD-Ce-RBC). This strategy is combined with photothermal therapy (PTT) for AD therapy. The application of RBC enhances the materials' biocompatibility and improves immune evasion. RBC-grown CeO₂, the first application in the field of AD, demonstrates outstanding antioxidant properties. CQD acts as a chelating agent for copper ions, which prevents the aggregation of Aβ. In addition, the thermal effect induced by near-infrared laser-induced CQD can break down Aβ fibers and improve the permeability of the blood-brain barrier. In vivo experiments on APP/PS1 mice demonstrate that CQD-Ce-RBC combined with PTT effectively clears cerebral amyloid deposits and significantly enhances learning and cognitive abilities, thereby retarding disease progression. This innovative multipathway approach under light-induced conditions holds promise for AD treatment.