Abstract
Gas therapy has been limited in its application as a robust standalone antitumor strategy due to the restricted gas production and cytotoxicity. To address this challenge, we employed electrotoxic PtRu composite metal nano-berries (PR) loaded with various therapeutic gas donors to construct a groundbreaking electric field-induced cascade gas therapy (EGT) platform, which generated a great electro-stress storm at tumor sites, exerting electrotoxicity and immunity functions against solid tumors, including those of large volume, through three pathways. Initially, electric field stimulation effectively boosted the release rate and yield of therapeutic gases from the EGT platform. Further, gas molecules reacted with reactive oxygen species (ROS) to either form oxidation coordination (CO and ROS) or generate more potent therapeutic components (RNS produced from ROS and NO), contributing to an electro-stress storm that augmented the cytotoxic potential of the gas components. Subsequently, this electro-stress storm further activated the tumor immune response, identifying and capturing escaped tumor cells, which held significant implications for treating tumors, including non-solid tumors with indistinct boundaries. In summary, the EGT platform leveraged an electro-stress storm to achieve ablation of large volume solid tumors and suppressed metastatic tumors, paving new pathways for gas-based therapeutic strategies.