Quercetin-derived red emission carbon dots: A multifunctional theranostic nano-agent against Alzheimer’s β-amyloid fibrillogenesis

Multifunctional agents with therapeutic and diagnostic capabilities are imperative to the prevention of Alzheimer's disease (AD), which is considered due to abnormal aggregation and deposition of β-amyloid protein (Aβ) as well as oxidative stress. Herein, quercetin (Que)- and p-phenylenediamine (p-PD)-derived red emission carbon dots (CDs) synthesized via a one-step hydrothermal method were designed as a novel theranostic nano-agent for the multi-target treatment of AD. R-CD-75 with an optimized composition exhibited significant inhibition of Aβ aggregation and rapid depolymerization of mature Aβ fibrils (<4 h) at micromolar concentrations (2 and 5 μg/mL, respectively). Moreover, R-CD-75 potently scavenged reactive oxygen species and showed turned-on red fluorescence imaging of Aβ plaques both in vitro and in vivo. In vitro assays proved that R-CD-75 significantly mitigated the Aβ-induced cytotoxicity and enhanced the cultured cell viability from 74.9% to 98.0%, while in vivo studies demonstrated that R-CD-75 prolonged the lifespan of AD nematodes by over 50% (from 13 to 20 d). Compared to the precursors Que and p-PD, R-CD-75 inherited some of their structures and functional groups, such as aromatic structures, phenolic hydroxyl and amino groups, which were considered to interact with Aβ species through hydrogen bonding, electrostatic interactions, hydrophobic interactions, and π-π stacking, thus contributing to its effectiveness in its theranostic functions. This research has opened a new avenue to the development of potent theranostic agents by designing novel carbon dots.