ATP-sensing DNA origami nanodevices for targeted modulation of purinergic signaling in inflammatory tissue injury

The pathophysiology of inflammatory illnesses is significantly influenced by purinergic signaling dysregulation, e.g., excessive extracellular ATP (exATP), yet current medication development efforts to inhibit purinergic receptors are inadequate. In a recent publication in Nature Communications, Li et al. [1] found that design and characterization of ATP-sensing DNA origami nanotubes (NTs) provide a novel method for metabolite sensing, utilizing ATP sensors and catalytic units (ENPP1/CD73). The innovative design led to reliable ATP binding and conversion to adenosine (ADO), supporting purinergic signaling modulation. Nanodevices (NDs) demonstrated effectiveness in sensing pathological exATP levels, crucial for purinergic receptor activation, significantly reducing cytokine expression and mitochondrial damage in immune cells. Monocyte-targeted ND delivery enhanced anti-inflammatory effects in acute lung and kidney injury models, showcasing superior therapeutic potential compared to unmodified NDs. RNA sequencing highlighted gene expression changes linked to inflammation, while metabolomic analysis showed improvements in mitochondrial function. The findings underscore the significance of purinergic signaling in inflammation and propose the DNA nanodevice as a promising therapeutic strategy, although challenges regarding stability and measurement remain to be addressed.