Five-in-One Neurodetoxification-Guardian-Type Near-Infrared Carbon Dots for Synergistic Blockade of Alzheimer's Disease Pathological Cascade.

Alzheimer's disease (AD) involves multiple interconnected pathologies, including amyloid-β (Aβ) aggregation, Cu2+ accumulation, oxidative stress, and mitochondrial dysfunction. Single-target therapies show limited efficacy, and most probes lack combined multipathology modulation and real-time imaging─often requiring extensive surface modifications for modest effects. Here, we report a simple five-in-one neuroprotective-guardian near-infrared luminescent carbon dots (NGN-CDs) synthesized via a glutathione-assisted solvothermal method in formamide. NGN-CDs enable simultaneous intervention in AD pathology and real-time monitoring without complex functionalization. Their strong negative surface charge suppresses Aβ aggregation and disaggregates preformed fibrils, reducing plaque deposition. The carboxyl-rich structure allows high-affinity Cu2+ chelation, blocking Cu2+-induced Aβ aggregation and reactive oxygen species (ROS) generation by inhibiting peroxidase-like activity. NGN-CDs also show dose-dependent broad-spectrum antioxidant activity, effectively scavenging ROS and alleviating oxidative stress. They selectively target mitochondria and preserve membrane potential under H2O2 or Aβ-Cu2+ challenge, protecting neuronal organelles. Their intrinsic near-infrared fluorescence at 685 nm enables stable, real-time visualization of AD-related processes. Standing out for its multifunctional synergy, this nanoprobe integrates five key functions─Aβ antiaggregation, Cu2+ detoxification, antioxidant activity, mitochondrial protection, and NIR imaging─into a single platform. This work presents an innovative strategy for synergistic AD intervention and a rational design framework for nanotheranostics in neurodegenerative diseases.