Regulating Tumor Metabolic Reprogramming with Biomimetic Co-Delivery of Simvastatin and Kynureninase for Immunotherapy.

ABSTRACT: The metabolic reprogramming of immunosuppressive tumor microenvironment (ITME) greatly influences the anti-tumor immunity. Bioinformatic analysis demonstrates that indoleamine 2,3-dioxygenase 1 and 3-hydroxy-3-methylglutaryl coenzyme A reductase (key enzymes of kynurenine (Kyn) and cholesterol metabolism, respectively), are overexpressed in human colon adenocarcinoma tissues. Herein, biomimetic and pH/ROS dual-responsive nanoparticles (PTSK@CRM) loaded with simvastatin and kynureninase (KYNase) are prepared to regulate Kyn and cholesterol metabolism, thereby enhancing the immunotherapeutic efficacy of PD-1 antibody (αPD-1). The monodisperse spherical PTSK@CRM is stable at pH 7.4, while it can release simvastatin and KYNase under low pH and high H₂O₂ concentration. PTS

SUBMITTER: Yin J 

PROVIDER: S-EPMC12948188 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature