Synergistic STING activation and oxidative cascades-induced ferroptosis drive tumor microenvironment remodeling by engineered manganese nanoreactors.

ABSTRACT: In head and neck squamous cell carcinoma, a "cold" (immune-desert) tumor microenvironment promotes immunosuppression, which is a critical driver of disease recurrence and therapeutic resistance. To address this challenge, we develop an innovative strategy to remodel the tumor immune microenvironment by disrupting intracellular redox balance to induce ferroptosis and immunogenic cell death, synergistically activating STING pathway to facilitating the transition of tumors from a "cold" to a "hot" immunophenotype. In this study, hyaluronic acid-functionalized hollow manganese dioxide nanoparticles loading β-lapachone (hMnL), engineered for targeted chemo-immunotherapy is constructed. In vitro investigations reveal that hMnL induces robust reactive oxygen species (ROS) generation, triggering f

SUBMITTER: Li W 

PROVIDER: S-EPMC12808843 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature