Manganese Amplifies Photoinduced ROS in Toluidine Blue Carbon Dots to Boost MRI Guided Chemo/Photodynamic Therapy

The contrast agents and tumor treatments currently used in clinical practice are far from satisfactory, due to the specificity of the tumor microenvironment (TME). Identification of diagnostic and therapeutic reagents with strong contrast and therapeutic effect remains a great challenge. Herein, a novel carbon dot nanozyme (Mn-CD) is synthesized for the first time using toluidine blue (TB) and manganese as raw materials. As expected, the enhanced magnetic resonance (MR) imaging capability of Mn-CDs is realized in response to the TME (acidity and glutathione), and r1 and r2 relaxation rates are enhanced by 224% and 249%, respectively. In addition, the photostability of Mn-CDs is also improved, and show an efficient singlet oxygen (1O2) yield of 1.68. Moreover, Mn-CDs can also perform high-efficiency peroxidase (POD)-like activity and catalyze hydrogen peroxide to hydroxyl radicals, which is greatly improved under the light condition. The results both in vitro and in vivo demonstrate that the Mn-CDs are able to achieve real-time MR imaging of TME responsiveness through aggregation of the enhanced permeability and retention effect at tumor sites and facilitate light-enhanced chemodynamic and photodynamic combination therapies. This work opens a new perspective in terms of the role of carbon nanomaterials in integrated diagnosis and treatment of diseases. Carbon dot nanozymes (Mn-CDs) are tumor microenvironment-responsive and create high contrast in tumors in magnetic resonance imaging (MRI). Importantly, under laser excitation, Mn-CDs have high singlet oxygen production and light-enhanced peroxidase-like activity, performing as photosensitizers and catalysts to produce reactive oxygen species to suppress tumor growth. In summary, Mn-CDs can be used for acidic glutathione-responsive MRI-guided/light-enhanced chemodynamic and photodynamic therapies.image