摘要
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.
基金
Shandong Traditional Chinese Medicine Technology Project,Grant/Award Number:Q-2023127
Innovation Project of Jinan Science and Technology Bureau,Grant/Award Number:2020GXRC022
Project for Scientific Research Innovation Team of Young Scholars in Colleges and Universities of Shandong Province,Grant/Award Numbers:2020KJC001,2022KJ196
National Natural Science Foundation of China,Grant/Award Number:22372091
Natural Science Foundation of Shandong Province,Grant/Award Number:ZR2023MB081。
