Cathepsin B (CTSB) is a cysteine protease usually confined to the lysosomes and employed as a biomarker in a wide range of solid tumors, correlating with increased invasiveness and poor prognosis.20, 21 We designed a nanoneedle sensor to detect the cytosolic activity of CTSB, anticipated to be minimal for healthy cells where CTSB is confined to the lysosomes, and increased for cancer cells where CTSB is aberrantly activated in the cytosol.22 The sensor consisted of a fluorescently labeled CTSB cleavable peptide covalently conjugated to a nanoneedle array (Figure1a). Here, CTSB is linked to cancer.