Zinc cyclic di-AMP nanoparticles target and suppress tumours via endothelial STING activation and tumour-associated macrophage reinvigoration.
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| Abstract |
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.
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| Authors | 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 |
| Journal | Nature nanotechnology (Nat Nanotechnol) Vol. 17 Issue 12 Pg. 1322-1331 (12 2022) ISSN: 1748-3395 [Electronic] England |
| PMID | 36302963 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't) |
| Copyright | © 2022. The Author(s), under exclusive licence to Springer Nature Limited. |
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