Tumor microenvironment–activated Zn//MnO2 battery for sustained and local electrochemical immunotherapy

Abstract

Metal ions are widely adopted to potentiate oxidative damage-induced immunogenic cell death (ICD) and regulate immune pathways. However, current ion delivery platforms lack precise administration over distribution and retention time within the tumor microenvironment, leading to high systemic toxicity and suboptimal therapeutic efficacy. Here, local electrochemical immunotherapy is developed by implanting a tumor microenvironment–activated Zn//MnO₂ battery, which uses body fluid as an electrolyte and endogenous glutathione as a redox mediator to promote sustained generation and localized retention of electrochemical products (Zn²⁺ and Mn²⁺). These elements trigger the ICD effect through reactive oxygen species accumulation and stimulate the STING pathway to activate immune cells effectively. Strategic placement of this battery around subcutaneous tumor sites results in a 99.6% growth inhibition rate after a 14-day treatment. This work demonstrates a powerful electrochemical tool for drug-free cancer immunotherapy, which may open an avenue for sustained and localized delivery of immune agonists.