ABSTRACT
Osteosarcoma (OS) is notorious for its high malignancy, and conventional chemotherapy drugs, while killing tumor cells, often inflict significant harm on the patient's body. The tumor microenvironment of OS is characterized by high levels of hydrogen peroxide (H2O2). Leveraging this feature, we have developed Mg-ZIF nanoparticles, which incorporate magnesium (Mg) to confer robust peroxidase (POD)-like enzymatic activity. These Mg-ZIF nanozymes can generate highly lethal superoxide anions within tumor cells in a responsive manner, thereby achieving effective tumor destruction. Both in vitro and in situ OS models have corroborated the anti-tumor efficacy of Mg-ZIF nanozymes, while also validating their biosafety. The design of Mg-ZIF nanozymes opens a new avenue for the treatment of OS, offering a promising therapeutic strategy.
ABSTRACT
Abnormal accumulation of hydrogen peroxide (H2O2) in the tumor microenvironment is associated with altered metabolism, abnormal proliferation of tumor cells, and changes in the tumor microenvironment. Based on this phenomenon, we have developed manganese-doped zeolitic imidazolate frameworks (Mn-ZIF) nanozymes, which exhibit superior peroxidase (POD)-like activity and enhanced cytotoxicity. Inside the tumor, the H2O2 is catalyzed by Mn-ZIF nanozymes through the Fenton reaction to generate more potent hydroxyl radicals (·OH), further increasing the local reactive oxygen species (ROS) levels in tumor cells and inducing tumor cell death. Meanwhile, the removal of H2O2 in the tumor microenvironment reduces tumor proliferation. We have confirmed the anti-tumor effect of these particles in an in situ osteosarcoma (OS) model, providing a direction for the future design of hybrid nanozyme drug delivery systems.
