Rational design of potent antioxidative agent with high biocompatibility is urgently needed to treat ischemic reperfusion-induced ROS-mediated cerebrovascular and neural injury during ischemia strokes. Here, we demonstrate an in situ synthetic strategy of bioactive zeolitic imidazolate framework-8–capped ceria nanoparticles (CeO₂@ZIF-8 NPs) to achieve enhanced catalytic and antioxidative activities and improved stroke therapeutic efficacy. This nanosystem exhibits prolonged blood circulation time, reduced clearance rate, improved BBB penetration ability, and enhanced brain accumulation, where it effectively inhibits the lipid peroxidation in brain tissues in middle cerebral artery occlusion mice and reduces the oxidative damage and apoptosis of neurons in brain tissue. CeO₂@ZIF-8 also suppresses inflammation- and immune response–induced injury by suppressing the activation of astrocytes and secretion of proinflammatory cytokines, thus achieving satisfactory prevention and treatment in neuroprotective therapy. This study also sheds light on the neuroprotective action mechanisms of ZIF-8–capped nanomedicine against reperfusion-induced injury in ischemic stroke.

Background: Radiotherapy is a commonly used tool in clinical practice to treat solid tumors. However, due to the unique microenvironment inside the tumor, such as high levels of GSH, overexpressed H₂O₂ and hypoxia, these factors can seriously affect the effectiveness of radiotherapy. Results: Therefore, to further improve the efficiency of radiotherapy, a core–shell nanocomposite CeO₂–MnO₂ is designed as a novel radiosensitizer that can modulate the tumor microenvironment (TME) and thus improve the efficacy of radiation therapy. CeO₂–MnO₂ can act as a radiosensitizer to enhance X-ray absorption at the tumor site while triggering the response behavior associated with the tumor microenvironment. According to in vivo and in vitro experiments, the nanoparticles aggravate the killing effect on tumor cells by generating large amounts of ROS and disrupting the redox balance. In this process, the outer layer of MnO₂ reacts with GSH and H₂O₂ in the tumor microenvironment to generate ROS and release oxygen, thus alleviating the hypoxic condition in the tumor area. Meanwhile, the manganese ions produced by degradation can enhance T1-weighted magnetic resonance imaging (MRI). In addition, CeO₂–MnO₂, due to its high atomic number oxide CeO₂, releases a large number of electrons under the effect of radiotherapy, which further reacts with intracellular molecules to produce reactive oxygen species and enhances the killing effect on tumor cells, thus having the effect of radiotherapy sensitization. In conclusion, the nanomaterial CeO₂–MnO₂, as a novel radiosensitizer, greatly improves the efficiency of cancer radiation therapy by improving the lack of oxygen in tumor and responding to the tumor microenvironment, providing an effective strategy for the construction of nanosystem with radiosensitizing function. Conclusion: In conclusion, the nanomaterial CeO₂–MnO₂, as a novel radiosensitizer, greatly improves the efficiency of cancer radiation therapy by improving the lack of oxygen in tumor and responding to the tumor microenvironment, providing an effective strategy for the construction of nanosystems with radiosensitizing function.