Metal coordination-driven assembly of stimulator of interferon genes-activating nanoparticles for tumor chemo-immunotherapy

Activating the stimulator of interferon genes (STING) signaling pathway is critical for enhancing antitumor immunity and remodeling the immunosuppressive tumor microenvironment (TME). Herein, we report the preparation of STING-activating nanoparticles via metal coordination-driven assembly of a synthetic STING agonist (i.e., SR717) and a chemotherapeutic drug (i.e., curcumin). After intravenous administration, the assembled nanoparticles could efficiently accumulate in tumors to improve the bioavailability of SR717 and trigger potent STING pathway activation for effective immune responses. Meanwhile, the released curcumin evokes immunogenic cell death in tumors and regulates amino acid metabolism by inhibiting the activation of indoleamine 2,3-dioxygenase 1, leading to the reversal of the immunosuppressive TME. The antitumor immunity induced by nanoparticles significantly inhibits the growth of primary, recurrent, and metastatic tumors. The assembled nanoparticles are promising for the co-delivery of STING agonists and drugs in improved tumor chemo-immunotherapy. STING-activating nanoparticles composed of agonists and chemotherapeutics are fabricated via metal coordination-driven assembly for combination chemo-immunotherapy. The nanoparticles effectively enhance the antitumor immunity through activating the STING pathway, inducing immunogenic cell death and downregulation of the amino acid metabolism, which can suppress tumor growth, recurrence, and metastasis. image