DNA/DMXAA/Metal-Organic Framework Activator of Innate Immunity for Boosting Anticancer Immunity.
Xiaojing ChenQianyun TangJinqiang WangYan ZhouFengqin LiYuexia XieXingang WangLing DuJunru LiJun PuQuanyin HuZhen GuPeifeng LiuPublished in: Advanced materials (Deerfield Beach, Fla.) (2023)
Immunotherapy has achieved revolutionary success in clinics, but it remains challenging for treating hepatocellular carcinoma (HCC) characterized by high vascularization. Here, we reported that metal-organic framework-801 (MOF-801) could be employed as stimulator of interferon genes (STING) through Toll-like receptor 4 (TLR4) not just 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 could coordinate with MOF-801 to self-assemble into a nanoparticle (MOF-CpG-DMXAA) that effectively delivered CpG ODNs and DMXAA to cells for synergistically improving the tumour microenvironment by reprogramming tumor-associated macrophages (TAMs), promoting dendritic cells (DCs) maturation as well as destroying tumour blood vessels. In HCC-bearing mouse models, we demonstrated that MOF-CpG-DMXAA triggered systemic immune activation and stimulated robust tumoricidal immunity, resulting in a superior immunotherapeutic efficiency in orthotopic and recurrent HCC. This article is protected by copyright. All rights reserved.
Keyphrases
- metal organic framework
- toll like receptor
- dendritic cells
- dna methylation
- nuclear factor
- immune response
- inflammatory response
- drug delivery
- genome wide
- induced apoptosis
- mouse model
- primary care
- cell cycle arrest
- gene expression
- circulating tumor
- regulatory t cells
- single molecule
- cell death
- cell proliferation
- pi k akt
- drug release
- drug induced