In Vivo Molecular Imaging of OGG1 Activity Using a Cyclic Cleavage-Amplified DNA Nanodevice

Clinically, risk stratification for neuroblastoma (NB) requires tumor tissue obtained through surgical resection or biopsy. However, in some patients with NB, these procedures are not feasible prior to initiating chemotherapy, precluding reliable risk stratification and evidence-based treatment selection, thereby adversely affecting event-free and overall survival. Therefore, a molecular imaging strategy based on an OGG1-responsive DNA nanodevice (Ox-tFNA) was developed for in vivo risk stratification of NB, independent of surgically resected or biopsied NB tissue. OGG1 (8-oxoguanine DNA glycosylase 1), a key enzyme associated with NB malignancy, predominantly localizes to the nucleus in normal cells, whereas it exhibits both cytosolic and nuclear expression in cancer cells. The 8-oxoguanine (8-oxoG) site of Ox-tFNA is specifically recognized and cleaved by OGG1, resulting in the separation of the fluorophore and quencher and thereby generating a fluorescence signal. Moreover, upon completion of one excision event, OGG1 is released and can initiate a subsequent round of cleavage, enabling cyclic signal amplification. Experimental findings demonstrate that Ox-tFNA exhibits rapid kinetics (within 15 min), high sensitivity (LOD: 0.5 × 10−8 U/mL), and exceptional specificity for OGG1. Notably, it can distinguish between mouse models inoculated with high-risk and low-risk NB tissues derived from patients, without being affected by surgically resected or biopsy samples, while also demonstrating excellent biocompatibility. Overall, Ox-tFNA enables activity-based OGG1 imaging and holds promise for improving the precision of risk stratification in NB.