Engineered DNA-Copper Double-Modified NIR Carbon Nanodots as Oxidative Stress Amplifier for Targeted Intracellular Production of Reactive Oxygen Species

Regulating redox homeostasis is an advanced and efficient approach for cancer treatment. Well-designed catalytic drugs, which can catalytic generation of reactive oxygen species (ROS) in targeted cells, minimizing side effects, are urgently needed. Here, we developed a near infrared (NIR) carbon dot-based oxidative stress amplifier (named AptCND-Cu) for targeted cellular imaging and intracellular generation of ROS. AptCND-Cu was designed and prepared through a controllable double-covalent modification of NIR CNDs with a DNA aptamer and Cu complex. Detailed characterization techniques, including TEM, AFM, XPS and DLS, were used to confirm the successful coupling of both oligomer aptamer and metal complex. The resulting AptCND-Cu owns superior tumor targeting, stable NIR fluorescence (FL) emission, good photostability, and stable copper delivery. We demonstrate that this material can deplete glutathione (GSH) and can amplify Cu-induced Fenton-like reaction eventually causing cell death in vitro. AptCND-Cu exhibit also long tumor retention time in tumor-bearing mice and enhanced body clearance. This work not only propose an alternative strategy to the multifunctionalization of red-emissive CNDs, by simply integrating DNA and ion-based catalytic drugs, but also broadens their uses in cancer catalytic nanomedicine.