A DNA/DMXAA/Metal-Organic Framework Activator of Innate Immunity for Boosting Anticancer Immunity.

Xiaojing Chen, Qianyun Tang, Jinqiang Wang, Yan Zhou, Fengqin Li, Yuexia Xie, Xingang Wang, Ling Du, Junru Li, Jun Pu, Quanyin Hu, Zhen Gu, Peifeng Liu

Advanced materials (Deerfield Beach, Fla.) 2023 Apr

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Immunotherapy has achieved revolutionary success in clinics, but it remains challenging for treating hepatocellular carcinoma (HCC) characterized by high vascularization. Here, it is reported that metal-organic framework-801 (MOF-801) can be employed as a stimulator of interferon genes (STING) through Toll-like receptor 4 (TLR4) not just as a drug delivery carrier. Notably, cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs) and 5, 6-dimethylxanthenone-4-acetic acid (DMXAA) STING agonist with vascular disrupting function coordinates with MOF-801 to self-assemble into a nanoparticle (MOF-CpG-DMXAA) that effectively delivers CpG ODNs and DMXAA to cells for synergistically improving the tumor microenvironment by reprogramming tumor-associated macrophages (TAMs), promoting dendritic cells (DCs) maturation, as well as destroying tumor blood vessels. In HCC-bearing mouse models, it is demonstrated that MOF-CpG-DMXAA triggers systemic immune activation and stimulates robust tumoricidal immunity, resulting in a superior immunotherapeutic efficiency in orthotopic and recurrent HCC. © 2023 Wiley-VCH GmbH.

Citation

Xiaojing Chen, Qianyun Tang, Jinqiang Wang, Yan Zhou, Fengqin Li, Yuexia Xie, Xingang Wang, Ling Du, Junru Li, Jun Pu, Quanyin Hu, Zhen Gu, Peifeng Liu. A DNA/DMXAA/Metal-Organic Framework Activator of Innate Immunity for Boosting Anticancer Immunity. Advanced materials (Deerfield Beach, Fla.). 2023 Apr;35(15):e2210440