Tumor Microenvironment-Responsive Nanoparticles Enhance IDO1 Blockade Immunotherapy by Remodeling Metabolic Immunosuppression.

ABSTRACT: The clinical efficacy of immune checkpoint blockade (ICB) therapy is significantly compromised in the metabolically disordered tumor microenvironment (TME), posing a formidable challenge that cannot be ignored in current antitumor strategies. In this study, TME-responsive nanoparticles (HMP1G NPs) loaded with 1-methyltryptophan (1-MT; an indoleamine 2,3-dioxygenase 1 [IDO1] inhibitor,) and S-nitrosoglutathione (GSNO; a nitric oxide donor) is developed to enhance the therapeutic efficacy of 1-MT-mediated ICB. The HMP1G NPs responded to H⁺ and glutathione in the TME, releasing Mn²⁺, GSNO, and 1-MT. The released Mn²⁺ catalyzed the production of abundant reactive oxygen species and nitric oxide from hydrogen peroxide and GSNO, and the generated nitric oxide, sy

SUBMITTER: Wang M 

PROVIDER: S-EPMC11791960 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature