STING-Activating Nanomedicines in Cancer Immunotherapy: Mechanisms, Design, and Therapeutic Outcomes

The cyclic GMP-AMP synthase stimulator of cGAS- STING cascade has emerged as a therapeutic approach for treatment of cancer. By modulating the immunosuppressive tumour microenvironment (TME), this innate immune sensing mechanism detects cytoplasmic double-stranded DNA and triggers the expression and secretion of type I interferons, thereby initiating robust antitumour immune responses. Despite the therapeutic potentials of conventional STING agonist, it faces challenges such as limited bioavailability, non-specificity and associated side effects. Nanoparticle-based delivery systems offer a transformative solution through surface modification and multifunctional design, enabling targeted delivery and controlled release. This review provides a comprehensive overview of recent advances in STING-activating nanoparticles. These platforms integrate chemotherapy with immunotherapy, enhance tumour inhibition, induce long-term immune memory, and potentiate immune checkpoint blockade. Collectively, these innovations demonstrate significant therapeutic potential across multiple malignancies, including breast, ovarian, pancreatic, colorectal, bladder, melanoma, and hepatocellular cancers, by reprogramming the immunosuppressive TME.