Reinvigorating CD8⁺ T cells through ADRB1 blockade using copper-propranolol nanoparticles for enhanced immune checkpoint blockade therapy.

ABSTRACT: Currently, colorectal cancer ranks third in terms of global cancer incidence and second in terms of cancer-related mortality, posing a significant therapeutic challenge. However, the efficacy of immunotherapy is limited by the immunosuppressive tumor microenvironment, which is driven in part by T cell exhaustion. Herein, a copper-propranolol nanoplatform (Cu-PN NPs) rationally engineered by coordinating copper ions with propranolol and stabilizing the complex via mPEG-SH self-assembly was initially constructed. This design enables the codelivery of copper ions and propranolol, achieving dual functions: inducing copper-dependent cell death (cuproptosis) and apoptosis to trigger immunogenic cell death (ICD), and blocking ADRB1 on T cells to reverse exhaustion and restore effector function. I

SUBMITTER: Weng B 

PROVIDER: S-EPMC12784565 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature