Exosome engineered upconversion nanoparticles with targeting moieties enhance Aβ aggregate clearance and mitigate neurotoxicity in Alzheimer’s disease

Abstract

Alzheimer’s disease is an increasingly prevalent neurodegenerative disorder characterized by the accumulation of misfolded Aβ aggregates. The efficacy of upconversion nanomaterials in photodynamic therapy has been proven, yet their applicability is constrained by their inherent toxicity. In this study, exosomes derived from stem cells, combined with targeting molecules, were utilized to encapsulate upconversion nanoparticles for targeted removal of pathogenic amyloid aggregates in Alzheimer’s disease. Evidence from AFM and TEM imaging, fluorescence spectroscopy, and cell-based experiments demonstrates that the clearance efficiency of amyloid aggregates is enhanced, and the cytotoxicity induced by misfolded Aβ aggregates is significantly reduced in nerve cells. Notably, the viability of neural PC12 cells is partially restored even in the presence of toxic amyloid aggregates.