LAUSR

A cathepsin B (Cat B)‐responsive optical nanoprobe is designed and prepared for report of HL60 differentiation into macrophage. A peptide sequence FRFK is linked to fluorescein (FITC) via the distant amino group of its lysine and N‐terminated with acrylic acid (AA) to yield a molecular fluorescent probe AA‐FRFK (FITC). The molecular probe is further embedded in poly(lactic‐co‐glycolic acid) (PLGA) to form a fluorescent nanoprobe AA‐FRFK (FITC)@PLGA. The resultant optical nanoprobe is degradable by lysosomal Cat B, which is expressed in macrophages with a level of 5–10 times of that in HL60 cells. As a result, a significant decrease in fluorescence intensity is associated with the differentiation process of HL60 to macrophage and can be used as an indication of the differentiation process. The findings may pave a way toward the development of a universal in vitro labeling strategy of exogenous stem cells for report of in vivo cell differentiation by a dual‐mode imaging modality involving optical imaging and magnetic resonance imaging.