Zinc cyclic di-AMP nanoparticles target and suppress tumours via endothelial STING activation and tumour-associated macrophage reinvigoration
| Autor: | Kaiting Yang, Wenbo Han, Xiaomin Jiang, Andras Piffko, Jason Bugno, Chuanhui Han, Sirui Li, Hua Liang, Ziwan Xu, Wenxin Zheng, Liangliang Wang, Jiaai Wang, Xiaona Huang, Jenny P. Y. Ting, Yang-Xin Fu, Wenbin Lin, Ralph R. Weichselbaum |
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| Rok vydání: | 2022 |
| Předmět: |
Biomedical Engineering
Endothelial Cells Membrane Proteins Bioengineering Condensed Matter Physics Adenosine Monophosphate Atomic and Molecular Physics and Optics Zinc Neoplasms Tumor-Associated Macrophages Cyclic AMP Humans Nanoparticles General Materials Science Electrical and Electronic Engineering |
| Zdroj: | Nature Nanotechnology. 17:1322-1331 |
| ISSN: | 1748-3395 1748-3387 |
| Popis: | The clinical utility of stimulator of interferon genes (STING) agonists has been limited due to poor tumour-targeting and unwanted toxicity following systemic delivery. Here we describe a robust tumour-targeted STING agonist, ZnCDA, formed by the encapsulation of bacterial-derived cyclic dimeric adenosine monophosphate (CDA) in nanoscale coordination polymers. Intravenously injected ZnCDA prolongs CDA circulation and efficiently targets tumours, mediating robust anti-tumour effects in a diverse set of preclinical cancer models at a single dose. Our findings reveal that ZnCDA enhances tumour accumulation by disrupting endothelial cells in the tumour vasculature. ZnCDA preferentially targets tumour-associated macrophages to modulate antigen processing and presentation and subsequent priming of an anti-tumour T-cell response. ZnCDA reinvigorates the anti-tumour activity of both radiotherapy and immune checkpoint inhibitors in immunologically 'cold' pancreatic and glioma tumour models, offering a promising combination strategy for the treatment of intractable human cancers. |
| Databáze: | OpenAIRE |
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