Dual-locking fluorescent nanoprobes for HAase-triggered carbon monoxide imaging in living cells

Fluorescent nanoprobes for carbon monoxide (CO) imaging emerged as an excellent tool for cancer diagnosis, but they are activated by single-biomarker. Herein, we developed a dual-locking fluorescent nanoprobe (HA-DMC) for HAase-triggered carbon monoxide imaging in the mitochondrion of the cancer cells. The fluorescent nanoprobes have “double locks” structures made of acetyl hyaluronic acid chains (hyaluronidase-triggered, first lock) as a barrier to form nanoparticles and the nitro group (CO-triggered, second lock) as intramolecular charge transfer (ICT) groups to quench the fluorescence of coumarin-pyridine derivative dyes. When the “locks” were only unlocked in sequence (from hyaluronidase to CO), a strong green fluorescence appeared for achieving cancer imaging. Meanwhile, the HA-DMC exhibited some satisfactory properties, such as mitochondria-targeting properties, excellent selectivity and sensitivity (24-fold), good water dispersibility, low detection limit (225 nM), and low cytotoxicity. Such features ensured that the HA-DMC could be successfully utilized for fluorescently imaging exogenous CO in the mitochondrion of living cells. In addition, the HA-DMC was successfully used to monitor exogenous and endogenous CO in vivo. We thus envision that HA-DMC is a promising platform for CO imaging in the mitochondrion of cancer cells and would promote the progress of fluorescent nanoprobes.