The Emerging Role of Nanocarrier-Based Delivery Systems for cGAS-STING Activation in Cancer Immunotherapy

Activation of the cGAS-STING pathway is a potential strategy to potentiate anti-tumor immunity. However, clinical translation of STING agonists such as cGAMP is hampered by poor targeting, enzymatic degradation, and systemic off-target toxicity. Nanocarrier-based drug delivery systems (nano-DDS) overcome these limitations by improving stability, bioavailability, and tumor-specific delivery. This review summarizes recent advances in lipid-based, polymeric, metallic, mesoporous silica, and exosomal for STING agonist delivery. These nanoplatforms enable precise drug delivery and controlled release, thereby significantly augmenting anti-tumor immune responses. We further discuss combination strategies of STING nanoagonists with radiotherapy, chemotherapy, phototherapy, and immune checkpoint inhibitors. Finally, we outline current challenges and future directions, including protein corona effects, scalable manufacturing, and personalized therapy.