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Zinc cyclic di-AMP nanoparticles target and suppress tumours via endothelial STING activation and tumour-associated macrophage reinvigoration

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Zinc cyclic di-AMP nanoparticles target and suppress tumours via endothelial STING activation and tumour-associated macrophage reinvigoration. / Yang, Kaiting; Han, Wenbo; Jiang, Xiaomin; Piffko, Andras; Bugno, Jason; Han, Chuanhui; Li, Sirui; Liang, Hua; Xu, Ziwan; Zheng, Wenxin; Wang, Liangliang; Wang, Jiaai; Huang, Xiaona; Ting, Jenny P Y; Fu, Yang-Xin; Lin, Wenbin; Weichselbaum, Ralph R.

In: NAT NANOTECHNOL, Vol. 17, No. 12, 12.2022, p. 1322-1331.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Yang, K, Han, W, Jiang, X, Piffko, A, Bugno, J, Han, C, Li, S, Liang, H, Xu, Z, Zheng, W, Wang, L, Wang, J, Huang, X, Ting, JPY, Fu, Y-X, Lin, W & Weichselbaum, RR 2022, 'Zinc cyclic di-AMP nanoparticles target and suppress tumours via endothelial STING activation and tumour-associated macrophage reinvigoration', NAT NANOTECHNOL, vol. 17, no. 12, pp. 1322-1331. https://doi.org/10.1038/s41565-022-01225-x

APA

Yang, K., Han, W., Jiang, X., Piffko, A., Bugno, J., Han, C., Li, S., Liang, H., Xu, Z., Zheng, W., Wang, L., Wang, J., Huang, X., Ting, J. P. Y., Fu, Y-X., Lin, W., & Weichselbaum, R. R. (2022). Zinc cyclic di-AMP nanoparticles target and suppress tumours via endothelial STING activation and tumour-associated macrophage reinvigoration. NAT NANOTECHNOL, 17(12), 1322-1331. https://doi.org/10.1038/s41565-022-01225-x

Vancouver

Yang K, Han W, Jiang X, Piffko A, Bugno J, Han C et al. Zinc cyclic di-AMP nanoparticles target and suppress tumours via endothelial STING activation and tumour-associated macrophage reinvigoration. NAT NANOTECHNOL. 2022 Dec;17(12):1322-1331. https://doi.org/10.1038/s41565-022-01225-x

Bibtex

@article{ed766a2c7cd9457e9a093cc26c17756e,
title = "Zinc cyclic di-AMP nanoparticles target and suppress tumours via endothelial STING activation and tumour-associated macrophage reinvigoration",
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.",
keywords = "Humans, Cyclic AMP, Tumor-Associated Macrophages, Zinc/pharmacology, Endothelial Cells, Membrane Proteins, Neoplasms/drug therapy, Nanoparticles/therapeutic use, Adenosine Monophosphate",
author = "Kaiting Yang and Wenbo Han and Xiaomin Jiang and Andras Piffko and Jason Bugno and Chuanhui Han and Sirui Li and Hua Liang and Ziwan Xu and Wenxin Zheng and Liangliang Wang and Jiaai Wang and Xiaona Huang and Ting, {Jenny P Y} and Yang-Xin Fu and Wenbin Lin and Weichselbaum, {Ralph R}",
note = "{\textcopyright} 2022. The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2022",
month = dec,
doi = "10.1038/s41565-022-01225-x",
language = "English",
volume = "17",
pages = "1322--1331",
number = "12",

}

RIS

TY - JOUR

T1 - Zinc cyclic di-AMP nanoparticles target and suppress tumours via endothelial STING activation and tumour-associated macrophage reinvigoration

AU - Yang, Kaiting

AU - Han, Wenbo

AU - Jiang, Xiaomin

AU - Piffko, Andras

AU - Bugno, Jason

AU - Han, Chuanhui

AU - Li, Sirui

AU - Liang, Hua

AU - Xu, Ziwan

AU - Zheng, Wenxin

AU - Wang, Liangliang

AU - Wang, Jiaai

AU - Huang, Xiaona

AU - Ting, Jenny P Y

AU - Fu, Yang-Xin

AU - Lin, Wenbin

AU - Weichselbaum, Ralph R

N1 - © 2022. The Author(s), under exclusive licence to Springer Nature Limited.

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

KW - Humans

KW - Cyclic AMP

KW - Tumor-Associated Macrophages

KW - Zinc/pharmacology

KW - Endothelial Cells

KW - Membrane Proteins

KW - Neoplasms/drug therapy

KW - Nanoparticles/therapeutic use

KW - Adenosine Monophosphate

U2 - 10.1038/s41565-022-01225-x

DO - 10.1038/s41565-022-01225-x

M3 - SCORING: Journal article

C2 - 36302963

VL - 17

SP - 1322

EP - 1331

IS - 12

ER -