Manganese-Based Immunostimulatory Metal-Organic Framework Activates the cGAS-STING Pathway for Cancer Metalloimmunotherapy

作者：Zheng, Sui-Juan; Yang, Mingfang; Luo, Jia-Qi; Liu, Rong; Song, Jie; Chen, Yao^*; Du, Jin-Zhi^*

来源：ACS Nano, 2023, 17(16): 15905-15917.

DOI：10.1021/acsnano.3c03962

• Cancer metalloimmunotherapy
• Manganese ions
• Metal-organic frameworks
• STING activation
• Immunostimulatory nanomaterials

Metal-organicframeworks (MOFs) show tremendous promisefor drug delivery due to their structural and functional versatility.However, MOFs are usually used as biologically inert carriers in mostcases. The creation of intrinsically immunostimulatory MOFs remainschallenging. In this study, a facile and green synthesis method isproposed for the preparation of a manganese ion (Mn2+)-basedimmunostimulatory MOF (ISAMn-MOF) for cancer metalloimmunotherapy.ISAMn-MOF significantly facilitates the activation of cyclic GMP-AMPsynthase-stimulator of interferon genes (cGAS-STING) related genesand signaling pathways in bone-marrow-derived dendritic cells (BMDCs).BMDCs treated with ISAMn-MOF secrete 4-fold higher type I interferonand 2- to 16-fold higher proinflammatory cytokines than those treatedwith equivalent MnCl2. ISAMn-MOF alone or its combinationwith immune checkpoint antibodies significantly suppresses tumor growthand metastasis and prolongs mouse survival. Mechanistic studies indicatethat ISAMn-MOF treatment facilitates the infiltration of stimulatoryimmune cells in tumors and lymphoid organs. This study provides insightinto the design of bioactive MOFs for improved cancer metalloimmunotherapy.

• 单位
  南开大学; y