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Five-in-One Neurodetoxification-Guardian-Type Near-Infrared Carbon Dots for Synergistic Blockade of Alzheimer's
Caiping Ding1, Yuhan Zhang1, Zikang Chen1
1Key Laboratory of Organosilicon Chemistry and Material Technology, Ministry of Education, Zhejiang Key Laboratory of Organosilicon Material Technology, College of Material, Chemistry and Chemical Engineering, Hangzhou Normal University, Hangzhou 311121, Zhejiang, China.
Abstract:
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.
Insights
This study introduces novel carbon dots that simultaneously combat Alzheimer's disease pathologies, including amyloid-β aggregation and oxidative stress, while enabling real-time imaging for neuroprotection.
Area of Science:
- Nanomaterials Science
- Neuroscience
- Biomedical Engineering
Background:
- Alzheimer's disease (AD) presents complex pathologies like amyloid-β (Aβ) aggregation, copper (Cu2+) accumulation, oxidative stress, and mitochondrial dysfunction.
- Current single-target therapies and imaging probes for AD show limited efficacy due to their inability to address multiple pathologies simultaneously or provide real-time monitoring.
- Existing probes often require complex surface modifications for modest therapeutic or diagnostic effects.
Purpose of the Study:
- To develop a simple, multifunctional nanoplatform for simultaneous intervention in AD pathologies and real-time monitoring.
- To design a near-infrared luminescent carbon dot (NGN-CD) capable of addressing key AD hallmarks without complex functionalization.
- To establish a rational design framework for nanotheranostics targeting neurodegenerative diseases.
Main Methods:
- Synthesis of near-infrared luminescent carbon dots (NGN-CDs) using a glutathione-assisted solvothermal method.
- Evaluation of NGN-CDs' ability to suppress Aβ aggregation, chelate Cu2+, scavenge reactive oxygen species (ROS), and protect mitochondrial function.
- Utilizing intrinsic near-infrared fluorescence for real-time visualization of AD-related processes.
Main Results:
- NGN-CDs effectively suppressed Aβ aggregation and disaggregated preformed fibrils due to their negative surface charge.
- Carboxyl-rich NGN-CDs chelated Cu2+, inhibiting Cu2+-induced Aβ aggregation and ROS generation.
- NGN-CDs demonstrated dose-dependent antioxidant activity, protected mitochondrial membrane potential, and enabled stable NIR imaging at 685 nm.
Conclusions:
- The developed NGN-CDs offer a synergistic five-in-one approach for Alzheimer's disease intervention, integrating Aβ anti-aggregation, Cu2+ detoxification, antioxidant activity, mitochondrial protection, and NIR imaging.
- This work presents an innovative strategy for synergistic AD treatment and a design blueprint for multifunctional nanotheranostics in neurodegenerative diseases.
- The NGN-CDs provide a simple yet effective platform for simultaneous pathological intervention and real-time monitoring in AD.
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