Nanogenerators Supplying Highly Toxic Reactive Oxygen Species for Antitumor Therapy and Immune Activation

In recent years, antitumor strategies based on reactive oxygen species (ROS) have received extensive attention but are limited due to the low efficiency of ROS production and unsatisfactory free radical toxicity. In this work, Na₂S₂O₈@Co-metal–organic framework (ZIF-67) @glucose oxidase (NZG) NPs were prepared to provide highly toxic ROS including •SO₄^– and •OH and used for the treatment of breast cancer. When NZG NPs entered the tumor tissue, the Co-based metal–organic framework (ZIF-67) was responsively broken in the acidic microenvironment, and the released GOx further promoted the generation of gluconic acid and H₂O₂, thus accelerating ZIF-67 cleavage and Na₂S₂O₈ release under lower pH. The highly toxic sulfate radical (•SO₄^–) converted from S₂O₈^2– could further combine with H₂O to produce •OH, thereby enriching the ROS species at the tumor site. The combination of •SO₄^– and •OH not only effectively induced the apoptosis of breast cancer cells but also reversed the immunosuppressive microenvironment at the tumor site. In summary, as a novel highly toxic ROS nanogenerator, NZG NPs provide efficient chemokinetic therapy and immune activation to promote tumor tissue ablation, providing a strategy for the development of antitumor ROS generators.