A double rare earth doped CD nanoplatform for nanocatalytic/starving-like synergistic therapy with GSH-depletion and enhanced reactive oxygen species generation

Abstract

Cancer has been one of the principal diseases threatening human health in the world. Traditional chemotherapy, radiotherapy and surgery in clinical applications have some disadvantages, such as inefficiency, low specificity, and serious side effects. Therefore, some emerging synergistic therapies have been developed for more accurate diagnosis and more efficient treatment of cancer. Herein, novel Ce–Gd@CDs–GOx nanozymes were obtained by combining magnetic resonance/fluorescence (MR/FL) imaging and nanocatalytic/starving-like synergistic therapy for tumor tissue imaging and efficient cancer treatment. The as-prepared Ce–Gd@CDs–GOx nanozymes with a diameter of 25.0 ± 0.8 nm exhibited favorable physiological stability, negligible toxicity, bright fluorescence and strong T₁-weighted MR imaging (MRI) performance (10.97 mM⁻¹ s⁻¹). Moreover, the nanozymes could not only cut off the nutrient supply of tumor cells, but also generate ROS to synergistically enhance antitumor efficacy. The coexistence of Ce³⁺/Ce⁴⁺ in Ce–Gd@CDs–GOx endowed them with attractive capacity for alleviating hypoxia and enhancing GSH consumption to induce the apoptosis of tumor cells. Furthermore, most of the 4T1 cells treated with Ce–Gd@CDs–GOx nanozymes were damaged in the CCK-8 and Calcein-AM/PI staining assays, indicating the excellent efficiency of intracellular synergistic therapy. In summary, this study offered a promising strategy to design a nanoplatform for MR/FL imaging-guided nanocatalytic and starvation-like synergistic therapy of cancer.