STING-targeted nanomedicine in combination cancer immunotherapy: From rational design to formulation engineering to...

Although STING agonists have shown potential in reversing the "cold" tumor microenvironment (TME) by activating the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, their efficacy as monotherapy remains limited, and combination therapies face challenges such as poor synergy, suboptimal timing, and safety concerns. Nanocarriers have evolved from passive drug delivery vehicles into active immunomodulatory platforms, providing critical support for precision combination therapy through co-loading of multiple agents, spatiotemporally coordinated release, and cell-specific targeting. This review delineates STING-centered combination immunotherapy through rational nanocarrier engineering, from physicochemical tuning to programmable delivery. We catalogue nanoplatforms for multi-agent co-encapsulation, examine surface targeting and temporal modulation. Finally, we analyze clinical translational barriers and advance solutions, hoping to offer insights into the clinical translation of nanocarrier-based STING-targeted combination immunotherapy.