Dual Channel Activatable Cyanine Dye for Mitochondrial Imaging and Mitochondria-Targeted Cancer Theranostics

Because mitochondria are the key regulators for many cellular behaviors and are susceptible to hyperthermia and reactive oxygen species, mitochondria-specific reagents for simultaneous targeting, imaging, and treatment are highly desirable in cancer theranostics. Herein, we developed a mitochondria-targeted cyanine dye IR825-Cl, which possesses two separated excitation wavelength channels for both red fluorescence imaging and near-infrared (NIR) photothermal therapy (PTT). For imaging, IR825-Cl rapidly entered cells and selectively targeted mitochondria. Although IR825-Cl was completely quenched in water, interestingly, this dye had a turn-on response of red fluorescence (610 nm) in mitochondria under 552 nm excitation due to its polarity-responsive fluorescence emission. More interestingly, IR825-Cl realized the selective mitochondrial staining of cancer cells over normal cells and thus served as an ideal fluorescent probe for identifying cancer cells in normal tissues, which is extremely beneficial for cancer theranostics. For PTT, we demonstrated that under 808 nm NIR laser irradiation, this dye efficiently converted optical energy into heat, realizing mitochondria-targeted photothermal cancer therapy. Collectively, this molecule realized both high fluorescence emission (quantum yield > 43%) and effective light-to-heat conversion (17.4%), enabling its applications for wash-free fluorescence imaging for mitochondria and highly efficient fluorescence imaging-guided PTT.