Ni Kaiyuan, Lan Guangxu, Chan Christina, Duan Xiaopin, Guo Nining, Veroneau Samuel S, Weichselbaum Ralph R, Lin Wenbin
Department of Chemistry, The University of Chicago, Chicago, IL 60637, USA.
These authors contributed equally to this work.
Matter. 2019 Nov 6;1(5):1331-1353. Epub 2019 Aug 28.
Checkpoint blockade immunotherapy (CBI) is effective in promoting a systemic immune response against some metastatic tumors. The reliance on the pre-existing immune environment of the tumor, however, limits the efficacy of CBI on a broad spectrum of cancers. Herein, we report the design of a novel nanoscale metal-organic layer (nMOL), Hf-MOL, for effective treatment of local tumors by enabling radiotherapy-radiodynamic therapy (RT-RDT) with low-dose X-rays and, when in combination with an immune checkpoint inhibitor, regression of metastatic tumors by re-activating anti-tumor immunity and inhibiting myeloid-derived suppressor cells. Owing to the reduced dimensionality, nMOLs allow facile diffusion of reactive oxygen species and exhibit superior RT-RDT effects. The synergy of Hf-MOL-enabled RT-RDT immune activation and anti-programmed death ligand 1 (anti-PD-L1) CBI led to robust abscopal effects on a series of bilateral models of colon, head and neck, and breast cancers and significant anti-metastatic effects on an orthotopic model of breast cancer.
检查点阻断免疫疗法（CBI）在促进针对某些转移性肿瘤的全身免疫反应方面是有效的。然而，对肿瘤预先存在的免疫环境的依赖限制了CBI对广泛癌症的疗效。在此，我们报告了一种新型纳米级金属有机层（nMOL）——铪金属有机层（Hf-MOL）的设计，它通过低剂量X射线实现放射治疗-放射动力疗法（RT-RDT）来有效治疗局部肿瘤，并且当与免疫检查点抑制剂联合使用时，通过重新激活抗肿瘤免疫和抑制髓源性抑制细胞来使转移性肿瘤消退。由于维度降低，nMOLs使活性氧易于扩散并表现出卓越的RT-RDT效果。由Hf-MOL实现的RT-RDT免疫激活与抗程序性死亡配体1（抗PD-L1）CBI的协同作用，在一系列结肠癌、头颈癌和乳腺癌双侧模型上产生了强大的远隔效应，并在乳腺癌原位模型上产生了显著的抗转移效果。
