A sustainable ROS cycle generator (SRCG) for tumor chemodynamic therapy

Chemodynamic therapy (CDT) provides an alternative strategy for tumor therapy. However, the insufficient generation of intratumoral reactive oxygen species (ROS) has been a key challenge encountered in the application and translation of CDT. Herein, we develop a sustainable ROS cycle generator (SRCG) capable of continuously producing ROS for high-efficiency tumor CDT. SRCG uses a porous metal‒organic framework material (Cu-ZIF8) as a carrier for concurrent delivery of glucose oxidase (GOX) and hyaluronidase (HAase). This approach results in a highly efficient nanoreactor, Cu-ZIF8@GOX@HAase (CZGH), capable of releasing GOX and HAase under acidic conditions to hydrolyze glucose and hyaluronic acid. The resulting products can react with the Cu ions in CZ to produce high concentrations of ROS, promoting tumor cell death. Furthermore, CZGH can degrade the extracellular matrix (ECM) and enhance tumor permeability, which facilitates its delivery and relieves hypoxia. This allows for the infiltration of glucose into the tumor, ensuring a sufficient glucose supply from the bloodstream to the SRCG system, and hence resulting in a sustainable ROS production. The effectiveness of SRCG in CDT has been demonstrated both <i>in vitro</i> and <i>in vivo</i> studies in a breast tumor mouse model, highlighting its potential as a groundbreaking approach for extensive tumor treatment.