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

  • Kaiting Yang (Shared first author)
  • Wenbo Han (Shared first author)
  • Xiaomin Jiang (Shared first author)
  • 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

Related Research units

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.

Bibliographical data

Original languageEnglish
ISSN1748-3387
DOIs
Publication statusPublished - 12.2022

Comment Deanary

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

PubMed 36302963