Nanoformulations of chemotherapeutic activators of the cGAS–STING pathway in tumor chemoimmunotherapy

Chemotherapeutic drugs to activate the cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS)–stimulator of interferon genes (STING) pathway have been exploited for tumor chemoimmunotherapy. The clinical translation of chemotherapeutic cGAS–STING activators is hindered by the lack of safe, efficient, and specific delivery strategies. Nanodrug delivery systems (NDDS) designed for reducing toxic effects and improving transport effectiveness potentiate in vivo delivery of chemotherapeutic cGAS–STING activators. cGAS–STING monotherapy often encounters tumor resistance without providing satisfactory therapeutic benefit; therefore combination therapy is desirable. This review describes NDDS strategies for surmounting delivery obstacles of chemotherapeutic cGAS–STING activators and highlights combinatorial regimens, which utilize therapeutics that work by different mechanisms, for optimal therapy.