Fluorinated prodrug-engineered nano-remodeler relieves tumor hypoxia for dual-enhanced ferroptosis-immunotherapy.

ABSTRACT: Ferroptosis is recognized as a form of regulated cell death characterized by iron-dependent lipid peroxidation and significant immunogenic properties. However, we observe that the hypoxic tumor microenvironment (TME) of solid tumors severely limits ferroptosis induction and antitumor immune responses, while simultaneously promoting programmed death-ligand 1 (PD-L1) expression, thereby further compromising tumor immunotherapy. Herein, we exploit a fluorinated prodrug-engineered nano-remodeler to reverse the hypoxic and immunosuppressive TME for enhancing ferroptosis/immunomodulation-driven antitumor therapy. The nano-remodeler is elaborately co-assembled by the disulfide-bonded fluorinated JQ1 prodrug (a PD-L1 inhibitor) and sorafenib (Sor, a ferroptosis inducer). As expected, the ferroptos

SUBMITTER: Lei J 

PROVIDER: S-EPMC12711668 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature