Design of Red Fluorescence Ce-Based Carbon Dots of High and Balanced Multiple Functions against Alzheimer's β-Amyloid Fibrillization

The intricate pathophysiology of Alzheimer's disease (AD), characterized by β-amyloid (Aβ) deposition, oxidative stress, and neuroinflammation, presents significant challenges for conventional single-target therapeutic approaches, thereby necessitating the development of innovative multifunctional theranostic strategies. Herein, red fluorescence cerium-based carbon dots (CCP-CD) were designed and synthesized via a one-step solvothermal method by purposely selecting curcumin (Cur) for inhibitory and anti-inflammatory effects, Ce(NO₃)₃·6H₂O for enhancing antioxidant activity, and p-phenylenediamine (p-PD) for modulating fluorescence property as precursors. The as-prepared CCP-CD potently suppressed Aβ fibrillization and strongly eliminated multiple reactive oxygen species (ROS) (·OH, O₂·-, DPPH·) at low concentrations (1-10 μg/mL). Moreover, CCP-CD facilitates detection of Aβ plaques through a turn-on red fluorescence mechanism for both in vitro and in vivo imaging and quantification. In vitro assays showed that CCP-CD markedly attenuated Aβ-induced cytotoxicity and increased cell viability from ∼60 to 95%, as well as exhibited excellent anti-inflammatory effects by reducing the levels of TNF-α and IL-6 in BV-2 cells. In vivo experiments revealed that CCP-CD effectively suppressed Aβ plaque formation in the AD nematodes and prolonged the lifespan from 13 to 20 d. The unique structural characteristics of CCP-CD, including its conjugated aromatic framework, reversible Ce³⁺/Ce⁴⁺ redox pair, and abundant O- and N-containing functional groups, facilitate balanced multiple therapeutic and diagnostic functions. The work has thus provided an exceptional nanoagent for detecting Aβ and fighting against Aβ-associated toxicities.