Blood-brain barrier permeable carbon nano-assemblies for amyloid-β clearance and neurotoxic attenuation

Abnormal amyloid β-protein (Aβ₄₂) fibrillation is a key event in Alzheimer's disease (AD), and photodynamic therapy (PDT) possesses great potential in modulating Aβ₄₂ self-assembly. However, the poor blood-brain barrier (BBB) penetration, low biocompatibility, and limited tissue penetration depth of existing photosensitizers limit the progress of photo-oxidation strategies. In this paper, novel indocyanine green-modified graphene quantum dot nano-assemblies (NBGQDs-ICGs) were synthesized based on a molecular assembly strategy of electrostatic interactions for PDT inhibition of Aβ₄₂ self-assembly process and decomposition of preformed fibrils under near-infrared light. Combining the small-size structure of graphene quantum dots and the near-infrared light-responsive properties of ICGs, the NBGQDs-ICGs could achieve BBB penetration under 808 nm irradiation. More importantly, the neuroprotective mechanism of NBGQDs-ICG was studied for the first time by AFM, which effectively weakened the adhesion of Aβ₄₂ aggregates to the cell surface by blocking the interaction between Aβ₄₂ and the cell membrane, and restored the mechanical stability and adhesion of the neuron membrane. Meanwhile, NBGQDs-ICG promoted phagocytosis of Aβ₄₂ by microglia. In addition, the good biocompatibility and stability ensured the biosafety of NBGQDs-ICG in future clinical applications. We anticipate that such multifunctional nanocomponents may provide promising avenues for the development of novel AD inhibitors.