biostudies-literatureYin JFundamental Research Funds of the Central Universities, ChinaDevelopment and Reform Commission of Jilin ProvinceNational Natural Science Foundation of ChinaScience and Technology Department of Jilin ProvinceNational Key Research and Development Program of Chinae08107https://www.ebi.ac.uk/biostudies/studies/S-EPMC12948188biostudies-literatureUnknown13(12)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. PTSAdvanced science (Weinheim, Baden-Wurttemberg, Germany)Regulating Tumor Metabolic Reprogramming with Biomimetic Co-Delivery of Simvastatin and Kynureninase for Immunotherapy.PMC129481882024-JCXK-11U24A203652023C0152023-JCXK-252024YFE021380032271319YDZJ202401328ZYTS52203168Liu ZZhao SSun SLi QYang SYin JfalseRegulating Tumor Metabolic Reprogramming with Biomimetic Co-Delivery of Simvastatin and Kynureninase for Immunotherapy.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. PTS2026-01-01T00:00:00Z2026 Feb2026-07-16T22:17:00.897Z2026-07-12T03:08:51.436ZS-EPMC129481884143205710.1002/advs.202508107