Spiropyran in Situ Switching: A Real-Time Fluorescence Strategy for Tracking DNA G‑Quadruplexes in Live Cells

DNA G-quadruplexes (G4s) in vivo have been linked to cancer and other diseases such as neurological disorders. Nondestructive fast detection of endogenous DNA G4s can provide specific real-time information, which is of particular interest for clinic accurate diagnosis. However, tools to probe live-cell endogenous DNA G4s in real time are very limited. Herein, we report the design and development of a fluorescent molecule QIN for the real-time detection of endogenous DNA G4s in live cells with the aid of a new spiropyran in situ switching (SIS) strategy. The lipophilic spiropyran-linked QIN differs from the other probes in that it can enter live cells readily within 15 s and can be in situ induced by DNA G4s to adopt its charged open form, causing a large red shift in the fluorescent emission wavelength. Live-cell super-resolution fluorescent imaging suggests that the SIS-based probe has high photostability and can be applied for the accurate detection of DNA G4s in complex biosystems with very high sensitivity and selectivity.