Tumor-Penetrating Hierarchically Structured Nanomarker 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 and are thus challenging to be detected directly from body fluids with high sensitivity and specificity, especially in the early stage of tumorigenesis. Here, we demonstrate an exogenous tumor-penetrating nanomarker composed of fluorescent nanoparticles conjugated with specific fluorescein-labeled peptides. The injectable nanomarkers perform four functions: they penetrate the 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 of the cyclic process of the nanomarker was also accomplished. The nanomarker can noninvasively diagnose and monitor tumors with a 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.