Tumor-penetrating hierarchically-structured nano-marker for imaging-guided urinary monitoring of cancer.

The capacity to diagnose cancer with the existing endogenous biomarkers remains limited because biomarkers usually act at the tumor site, thus, is challenging to detect directly from body fluids with high sensitivity and specificity especially in the early stage of tumorigenesis. Here we demonstrate an exogenous tumor-penetrating nano-marker composed of fluorescent nanoparticles conjugated with specific fluorescein-labelled peptides. The injectable nano-markers perform four functions: they penetrate tumor, target sites of cancer, cleave specific peptides by on-target protease and drop off the labeled peptide into host urine for fluorescent detection. Sensitive in vivo tracking and monitoring cyclic process of the nano-marker was also accomplished. The nano-marker can noninvasively diagnose and monitor tumor with the volume of about 17 mm3 without invasive core biopsies. Enhanced capacity of early point-of-care detection for cancer is accomplished by receptor-dependent specificity of the signal generation in the urine, compared with clinically used blood biomarkers.