Metabolically Stable Chimeric Nucleic Acid Nanoprobe Artificial Biomarker for Cancer Urine Biopsy

Urine biopsy based on in vitro probes has emerged as a promising method for disease diagnosis. Here, a nanoprobe (designated as GTP) was developed by functionalizing nanomaterials with a chimeric nucleic acid (comprising peptide nucleic acid (PNA) and DNA) and integrating it with an electrochemical biosensor for cancer diagnosis via urine biopsy. The GTP specifically responded to telomerase (TE) at tumor sites, releasing metabolically stable PNA reporters of GTP into the blood circulation. By further leveraging the high affinity of the PNA for hybridization, the PNA reporters in urine were sensitively quantified on an electrochemical surface, effectively translating in situ tumor marker information into detectable in vitro signals. Relying on the combination of GTPs and the electrochemical biosensor, triple-negative breast cancer in xenograft mice could be diagnosed as early as day 6 post-transplantation. The electrochemical urine biopsy demonstrated significant clinical potential for moving forward the diagnostic window and quantitatively monitoring cancer progression.