Cleavable bimetallic-organic polymers for ROS mediated cascaded cancer therapy under the guidance of MRI through tumor hypoxia relief strategy

Despite recent advances in tumor treatment, reactive oxygen species (ROS)-mediated therapy, such as photodynamic therapy (PDT) and chemical dynamic therapy (CDT), remains challenging mainly due to hypoxia in tumor microenviroment. Relieving the hypoxia of tumor tissue has been considered as an attractive strategy for enhancing efficacy of ROS-based cancer treatment. Herein, one cascaded platform was developed to overcome tumor hypoxia and synergistically enhance the effect of ROSmediated therapy. This platform is based on cleavable bimetallic metal organic polymers (DOX@Fe/Mn-THPPTK-PEG). As an efficient Fenton-like material, it could not only produce cytotoxic center dot OH by catalyzing the decomposition of intracellular H2O2, but also generate O-2 to alleviate tumor hypoxia. In addition, the DOX-loaded metal organic polymers (MOPs could be disrupted after being exposed to laser irradiation or/and treated with H2O2, and then release the DOX for chemotherapy. Overall, 3 therapies (hypoxia-relieved PDT, photo-enhanced CDT, and ROS-mediated chemotherapy) could be achieved simultaneously by such a smart platform. Furthermore, T-1-weighted MRI imaging ability of the MOPs could be greatly improved under H2O2 treatment. Therefore, total four robust functions were realized in a simple platform. These findings demonstrate great clinical potentials of the MOPs for cancer theranostics.