Spatially Preorganized Hybridization Chain Reaction for the Prompt Diagnosis of Inflammation

Biological systems utilize precise spatial organization to facilitate and regulate information transmission within signaling networks. Inspired by this, artificial scaffolds that enable delicate spatial arrangements are desirable to increase the local concentration of reactants, expedite specific interactions, and minimize undesired interference. In this study, we presented an integrated biosensing nanodevice, termed TRI-HCR, in which hybridization chain reaction (HCR) probes were precisely organized on a triangular DNA origami nanostructure (TRI) with finely-tuned distance, quantity, and pattern. Compared to traditional HCR in the free form, this nanodevice demonstrated increased reaction rate and signal level. We further employed the optimized TRI-HCR for in vivo imaging of a nucleic acid biomarker of inflammatory diseases. In both acute gouty arthritis (AGA) and sepsis-associated acute kidney injury (SA-AKI) model mice, TRI-HCR was capable of diagnosing inflammation in the early stages, significantly earlier than histological examination. We anticipate that this precise spatial preorganization strategy for HCR holds promise for broader applications in early disease detection and monitoring.