Immunostimulatory effects of IL-12 targeted pH-responsive nanoparticles in macrophage-enriched 3D immuno-spheroids in vitro model.

ABSTRACT: Metastatic colorectal cancer (CRC) has the dismal 5-year survival rate of only 14%, and immunotherapies fail to improve the patient outcome. One reason for the poor response rate is the slightly acidic (~ 6.5) immunosuppressive microenvironment. Interleukin 12 (IL-12) is a highly potent pro-inflammatory cytokine that can stimulate tumor immune cells and reverse immunosuppression by inducing interferon gamma (IFN-γ) expression. However, its clinical applications are hindered by systemic side effects. In this study, we developed pH-responsive polymeric nanoparticles (NPs) encapsulating IL-12 to enhance its therapeutic efficacy into the tumor microenvironment (TME). IL-12-loaded pH-responsive NPs induced antitumoral pro-inflammatory response in macrophages at pH ~ 6.5, determined by increased

SUBMITTER: Silveira MJ 

PROVIDER: S-EPMC12619765 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature