Glutamine Antagonist Synergizes with Electrodynamic Therapy to Induce Tumor Regression and Systemic Antitumor Immunity

Electrodynamic therapy (EDT) combining nanotechnology with electronic current was used in this study to generate highly cytotoxic oxidative hydroxyl radicals (·OH) for tumor destruction. However, increasing evidence suggests that EDT treatment alone for one time still faces great challenges in achieving long-term tumor suppression in an immunosuppressive environment, which would raise the risk of later tumor recurrence. Benefitting from the marvelous potential of reactive oxygen species (ROS)-mediated dynamic therapies in tumor immunocombination therapy due to their immunogenic cell death (ICD) effect, a glutamine antagonist 6-diazo-5-oxo-l-norleucine (DON)-loaded nanocarrier (Pt–Pd@DON) was designed for combination therapy (EDT and immunotherapy) against tumor recurrence and metastasis. The protective immune response was motivated in highly immunosuppressive tumors by the joint functions of ICD and CD8+ T cell infiltration promoted by DON. A great therapeutic efficacy has been demonstrated in primary and metastatic tumor models, respectively. This study has provided an effective thought way for clinical highly immunosuppressive tumor treatment.