促炎细胞因子
金属有机骨架
免疫系统
癌症研究
干扰素基因刺激剂
化学
癌细胞
信号转导
干扰素
细胞生物学
癌症
材料科学
生物
先天免疫系统
炎症
免疫学
遗传学
有机化学
吸附
作者
Sui-Juan Zheng,Mingfang Yang,Jia‐Qi Luo,Rong Liu,Jie Song,Yao Chen,Jin‐Zhi Du
出处
期刊:ACS Nano
[American Chemical Society]
日期:2023-08-11
卷期号:17 (16): 15905-15917
被引量:13
标识
DOI:10.1021/acsnano.3c03962
摘要
Metal–organic frameworks (MOFs) show tremendous promise for drug delivery due to their structural and functional versatility. However, MOFs are usually used as biologically inert carriers in most cases. The creation of intrinsically immunostimulatory MOFs remains challenging. In this study, a facile and green synthesis method is proposed for the preparation of a manganese ion (Mn2+)-based immunostimulatory MOF (ISAMn-MOF) for cancer metalloimmunotherapy. ISAMn-MOF significantly facilitates the activation of cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) related genes and signaling pathways in bone-marrow-derived dendritic cells (BMDCs). BMDCs treated with ISAMn-MOF secrete 4-fold higher type I interferon and 2- to 16-fold higher proinflammatory cytokines than those treated with equivalent MnCl2. ISAMn-MOF alone or its combination with immune checkpoint antibodies significantly suppresses tumor growth and metastasis and prolongs mouse survival. Mechanistic studies indicate that ISAMn-MOF treatment facilitates the infiltration of stimulatory immune cells in tumors and lymphoid organs. This study provides insight into the design of bioactive MOFs for improved cancer metalloimmunotherapy.
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