Illuminating the tumor microenvironment with organelle-specific fluorescent probes

The microenvironment is essential for the proper functioning of biomolecules, subcellular organelles, cells, and organisms as a whole. In particular, the physical characteristics of the cellular microenvironment, such as polarity, viscosity, and pH, have a significant impact on cellular processes and disease progression. These parameters are crucial in regulating cellular activities, influencing both normal physiological functions and pathological changes. As a result, any disruption or imbalance in the microenvironment can contribute to the onset and development of various diseases, including cancer.

Herein, a series of fluorescent probes (N-1, N-2, N-3, N-4, N-5, and N-6) were designed and synthesized based on pyridine, quinoline, and acridine units to detect changes in the microenvironment. These probes, characterized by high selectivity and sensitivity, were evaluated for their ability to detect viscosity, pH, and polarity. Among them, N-1 was capable of monitoring variations in pH and viscosity through different channels, N-4 exhibited highly sensitive to viscosity changes, and N-6 was able to detect shifts in polarity. Interestingly, N-1 co-localized with lysosomes and successfully detected pH changes as well as viscosity alterations induced by nystatin and rapamycin within the lysosomes. N-4 effectively targeted the cell membrane and detected viscosity changes. Importantly, both N-1 and N-4 selectively illuminated cancerous lysosomes and cell membranes with intense red fluorescence, demonstrating their effectiveness in distinguishing cancerous cells or tissues from normal cells or tissues.

Monitoring the microenvironment within specific organelles is critical for gaining a deeper understanding of organelle interactions and their roles in cellular function. This research is not only essential for elucidating fundamental cellular processes but also plays a key role in advancing the clinical diagnosis and treatment of diseases linked to organelle dysfunction.