Chiral carbon dots based on ternary carbon sources: A multifunctional therapeutic agent for Cu2+-induced Alzheimer's disease

Metal dyshomeostasis is one of the pathological features of Alzheimer's disease (AD). Cu2+ is believed to induce the formation of neurotoxic β-amyloid (Aβ) aggregates and aggravate oxidative damage. It is challenging to take effective therapeutic interventions towards the complicated pathogenesis related to Cu2+. Herein, chiral carbon dots were proposed for Cu2+-related AD therapy. The chiral CDs were prepared based on the ternary carbon sources, using L/d-cysteine as the chiral carbon source, citric acid as the carbonization source and β-cyclodextrin as the chirality inducer, reserving and enhancing the chirality of CDs. Compared to L-Cys-CDs, D-Cys-CDs exhibited enhanced chirality, stronger affinity towards Cu2+ and comparable antioxidant ability, but better inhibition on peroxidase-like activity of Cu2+ or Aβ42-Cu2+. Thus, D-Cys-CDs performed better to inhibit Cu2+-induced Aβ aggregation. Meanwhile, D-Cys-CDs can alleviate the cytotoxicity of Aβ42-Cu2+ with satisfactory anti-inflammation effect and scavenging ability towards intracellular reactive oxygen species. D-Cys-CDs succeeded in reducing Aβ deposits and releasing paralysis for the AD model CL2120 nematodes. D-Cys-CDs with an enantiomeric effect on Cu2+-induced Aβ aggregation and the peroxidase-like activity of Cu2+ was promising as the multifunctional therapeutic agent for Cu2+-induced AD therapy.