A synthetic urinary probe-coated nanoparticles sensitive to fibroblast activation protein [alpha] for solid tumor diagnosis

We developed fibroblast activation protein [alpha] (FAP[alpha])-sensitive magnetic iron oxide nanoparticles (MNPs) by conjugating a substrate-reporter tandem peptide as a synthetic biomarker to the surface of MNPs (marker-MNPs). In vitro, the marker-MNPs showed stability when treated with serum or urine and exhibited high susceptibility and specificity for FAP[alpha] enzyme and 3T3/FAP[alpha] cell line. Furthermore, the marker-MNPs were administered to esophageal squamous cell carcinoma xenograft tumor mice; they reached the tumor tissues in the mice, where they were cleaved effectively by the local overexpressed FAP[alpha] to release the reporter peptide and filter it into the urine. The tumor targeting and biodistribution of marker-MNPs were verified by in vivo imaging. The cleaved reporter peptides in urine detected by enzyme-linked immunosorbent assay have high diagnostic accuracy for esophageal squamous cell carcinoma (area under the receiver-operating characteristic curve =1.0). Our study implies a promising strategy of utilizing the low-cost and noninvasive synthetic urinary probe-coated nanoparticles for the diagnosis of FAP[alpha]-positive solid tumors, except for in renal cancer. Keywords: synthetic urinary probe, magnetic iron oxide nanoparticles, fibroblast activation protein [alpha], tumor diagnosis