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.

干扰素基因刺激剂 (STING) 激动剂的临床应用由于肿瘤靶向性差和全身给药后的不良毒性而受到限制。在这里，我们描述了一种强大的肿瘤靶向 STING 激动剂 ZnCDA，它是通过将细菌衍生的环状二聚磷酸腺苷 (CDA) 包裹在纳米级配位聚合物中形成的。静脉注射 ZnCDA 可延长 CDA 循环并有效靶向肿瘤，以单次剂量在多种临床前癌症模型中发挥强大的抗肿瘤作用。我们的研究结果表明，ZnCDA 通过破坏肿瘤脉管系统中的内皮细胞来增强肿瘤积聚。ZnCDA 优先靶向肿瘤相关巨噬细胞以调节抗原加工和呈递以及随后引发抗肿瘤 T 细胞反应。