A supramolecular biosensor for monitoring lysosomal DNase activity in vivo and identifying tumor cells by responding to G-quadruplex hydrolysis

Lysosomal DNase is essential for maintaining cellular DNA synthesis and metabolic homeostasis, and their abnormal activity leads to a variety of diseases such as cancer and immune abnormalities. Herein, a biosensor named PTC-G4 has been constructed to detect lysosomal DNase activity in solution and living organisms. This biosensor consists of a cyanine dye (PTC) supramolecule and an exogenous G-quadruplex (G4) DNA, both of which are highly targeted to lysosomes in live cells, while PTC is highly specific for the G4 structure. Lysosomal DNase activity was evaluated by monitoring the double-channel fluorescence of PTC monomers and aggregates in response to G4 hydrolysis. PTC-G4 can not only be used as a tool for monitoring lysosomal DNase in vivo, but also can distinguish the difference between tumor cells and normal cells, making it promising in tumor screening or auxiliary diagnosis.