Mitochondria/lysosome dual-organelle labelling esterase probe for monitoring cell viability and evaluating lung cancer drug efficiency

Monitoring of cell viability plays a key role in cancer therapy and evaluation of drug efficiency. Mitochondria and lysosomes are involved in regulating cell viability in many biological processes such as apoptosis, necrosis, autophagy, and cell proliferation. Thus, there is an emerging interest in the real-time evaluation of cell viability in both mitochondria and lysosomes. Herein, for the first time, we rationally designed and developed a mitochondria/lysosome dual-organelle labelling esterase-responsive ratiometric fluorescent probe, named TMLE-2, for dual-channel monitoring of cell viability and evaluation of lung cancer drug efficiency. TMLE-2 showed dramatic ratio fluorescence changes (about 51-fold) upon reacting with esterase. Furthermore, TMLE-2 enabled visualization of mitochondria and lysosomes with red and green emission, respectively; moreover, H₂O₂-induced cell damage, sorafenib-induced ferroptosis and ascorbic-acid-mediated cell protective effects were successfully assessed by dual-organelle ratiometric fluorescent imaging and flow cytometry data. More importantly, TMLE-2 was successfully used for the first time to evaluate the efficiency of lung cancer drugs at the cellular and tissue levels based on dual-organelle esterase activity assay. In summary, the newly designed TMLE-2 is expected to have enormous potential for facilitating advancements in biomedical fields related to cell viability.