The uptake of the cathepsin B-responsive nanoparticle in SCC7 murine squamous cell carcinoma was accompanied by increasing red fluorescence, which colocalized with the green fluorescence for immunohistochemical detection of cellular cathepsin B. The cell-associated Cy5.5 fluorescence signal could be blocked by treatment with 1b and the particulate probe resulted in stronger NIR fluorescence than the isolated, soluble quenched peptide. This evidence concerns the gene CTSB and squamous cell carcinoma.