Nanogenerators Supplying\nHighly Toxic Reactive Oxygen\nSpecies for Antitumor Therapy and Immune Activation

In recent years, antitumor strategies based on reactive\noxygen\nspecies (ROS) have received extensive attention but are limited due\nto the low efficiency of ROS production and unsatisfactory free radical\ntoxicity. In this work, Na<sub>2</sub>S<sub>2</sub>O<sub>8</sub>@Co-metal–organic\nframework (ZIF-67) @glucose oxidase (NZG) NPs were prepared to provide\nhighly toxic ROS including •SO<sub>4</sub><sup>–</sup> and •OH and used for the treatment of breast cancer. When\nNZG NPs entered the tumor tissue, the Co-based metal–organic\nframework (ZIF-67) was responsively broken in the acidic microenvironment,\nand the released GOx further promoted the generation of gluconic acid\nand H<sub>2</sub>O<sub>2</sub>, thus accelerating ZIF-67 cleavage\nand Na<sub>2</sub>S<sub>2</sub>O<sub>8</sub> release under lower pH.\nThe highly toxic sulfate radical (•SO<sub>4</sub><sup>–</sup>) converted from S<sub>2</sub>O<sub>8</sub><sup>2–</sup> could\nfurther combine with H<sub>2</sub>O to produce •OH, thereby\nenriching the ROS species at the tumor site. The combination of •SO<sub>4</sub><sup>–</sup> and •OH not only effectively induced\nthe apoptosis of breast cancer cells but also reversed the immunosuppressive\nmicroenvironment at the tumor site. In summary, as a novel highly\ntoxic ROS nanogenerator, NZG NPs provide efficient chemokinetic therapy\nand immune activation to promote tumor tissue ablation, providing\na strategy for the development of antitumor ROS generators.