The clinical utility of stimulator of interferon genes (STING) agonists has been limited due to poor tumor-targeting and unwanted toxicities following systemic delivery. Here we describe a robust tumor-targeted STING agonist, ZnCDA, formed by the encapsulation of bacterial-derived cyclic dimeric adenosine monophosphate (CDA) in nanoscale coordination polymers. Intravenously injected ZnCDA prolonged CDA circulation and efficiently targeted tumors, mediating robust antitumor effects in a diverse set of preclinical cancer models. Our findings reveal ZnCDA enhances tumor accumulation through disrupting endothelial cells in the tumor vasculature. Once in the tumor, ZnCDA preferentially targets tumor associated macrophages to modulate antigen processing/presentation and subsequent priming of an antitumor T cell response. ZnCDA reinvigorated the antitumor activity of both radiotherapy and immune checkpoint inhibitors in immunologically “cold” pancreatic and glioma tumor models, offering a promising combination strategy for the treatment of intractable human cancers.

Nanoscale coordination polymers deliver immuno modulators for cancer immunology

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