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

作　　者：Guiqiang Zhang Ning Wang Yuan Ma Shumei Zhai To Ngai Shilei Ni Xinyi Jiang Jianwei Jiao Jiwei Cui 

机构地区：[1]Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education,School of Chemistry and Chemical Engineering,Shandong University,Jinan,China [2]Medical Science and Technology Innovation Center,Shandong First Medical University&Shandong Academy of Medical Sciences,Jinan,China [3]Department of Neurosurgery,Qilu Hospital and Institute of Brain and Brain-Inspired Science,Cheeloo College of Medicine,Shandong University,Jinan,China [4]Department of Chemistry,The Chinese University of Hong Kong,Hong Kong,China [5]Department of Pharmaceutics,School of Pharmaceutical Sciences,Cheeloo College of Medicine,Shandong University,Jinan,China

出　　处：《BMEMat(BioMedical Engineering Materials)》2024年第2期118-133,共16页生物医学工程材料（英文）

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。

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.

关 键 词：amino acid metabolism immunotherapy NANOPARTICLES self-assembly STING 

分 类 号：R730.51[医药卫生—肿瘤] R318[医药卫生—临床医学]