Metabolic nanoblockers for synergistic cancer treatment through glutaminase inhibition and sonodynamic therapy.

ABSTRACT: The immunotherapeutic potential of sonodynamic therapy (SDT) is hindered by tumor defense mechanisms driven by glutamine metabolism, including glutathione (GSH)-dependent redox homeostasis and an immunosuppressive tumor microenvironment (TME). To address these challenges, we herein developed metabolic nanoblockers (CBE@AM NPs) by encapsulating a glutamine metabolism inhibitor CB839 and a sonosensitizer chlorin e6 (Ce6) into melanin-inspired nanoparticles. The resulting nanoblockers triggered robust reactive oxygen species (ROS) production upon ultrasound irradiation, thereby destroying tumor cells and inducing immunogenic cell death (ICD). Concurrently, they inhibited the glutamine metabolism in the tumor, disrupting redox homeostasis and remodeling the immunosuppressive TME, thereby ampli

SUBMITTER: Zhao W 

PROVIDER: S-EPMC12666580 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature