"Emerging precision drug delivery systems for controlled activation of the cGAS-STING pathway in Cancer, infection,...

The cyclic GMP-AMP synthase Stimulator of Interferon Genes (cGAS-STING) pathway is a key component of innate immunity, detecting cytosolic DNA and initiating type I interferon (IFN-I) responses that shape downstream adaptive immunity. Owing to its central role in antiviral defense, tumor immunosurveillance, and inflammatory regulation, STING has emerged as a promising therapeutic target across oncology, infectious diseases, neuroinflammation, and autoimmune disorders. However, the clinical translation of STING agonists and antagonists is constrained by poor pharmacokinetics, rapid systemic clearance, off-target cytokine release, and inefficient cytosolic delivery. To address these barriers, a diverse set of delivery technologies including lipid nanoparticles, polymeric carriers, inorganic nanomaterials, hydrogels, biologically derived vectors, and antibody STING conjugates has been developed to improve selective uptake, endosomal escape, pHarmacological stability, and tissue-specific accumulation. This review systematically examines these platforms, highlighting their mechanisms, immunological effects, advantages, limitations, and stages of clinical progression. Emerging innovations such as stimuli-responsive delivery systems, mRNA encoded STING modulators, virus-like particle (VLP) technologies, carrier-free nanocomplexes, and cell-based delivery approaches are also discussed for their potential to enable precise, tunable, and context-specific modulation of the cGAS-STING axis. Collectively, these advances represent a significant evolution in STING-targeted therapy, providing new opportunities to harness innate immunity and expand therapeutic applications across a broad spectrum of disease settings.