A highly permeable nanoplatform based on functionalized carbon dots for synergistic reactive oxygen/nitrogen species tumor therapy

Reactive oxygen species (ROS)-based antitumor strategies, particularly chemodynamic therapy, have garnered considerable attention. However, challenges such as difficulties in achieving deep penetration, relatively low H₂O₂ levels in the tumor microenvironment, the requirement for low pH by the Fenton reaction, and their short lifespan have impeded satisfactory therapeutic outcomes. Hence, we have developed a nanoplatform with enhanced permeability that not only generates significant amounts of ROS but also converts them into longer-lasting reactive nitrogen species (RNS), thereby improving tumor therapy efficacy. In our study, carbon dots were functionalized by doping with gold atoms and grafting nitrosoglutathione (GSNO) to form ACN, which exhibits glucose oxidase-like properties and enables laser-responsive NO release. ACN and indocyanine green (ICG) were then loaded onto MnO₂ nanoflowers to form MnO₂@AI. Upon arrival at the tumor site, MnO₂ reacts with H₂O₂ and GSH, leading to its degradation and the subsequent release of ACN, which is characterized by three permeation-promoting properties: ultra-small size, positive charge, and NO content. In addition, ACN promotes H₂O₂ production through glucose metabolism and reduces pH, both of which enhance the Fenton-like reaction of MnO₂, thereby amplifying ROS generation. The ICG in MnO₂@AI enhances its photothermal properties, leading to the responsive release of NO from GSNO grafted onto ACN, which then reacts with the increased ROS to generate more toxic RNS. Collectively, the approach described herein offers substantial potential for advancing the treatment of malignant tumors.