Bio-imaging with a group of acid-responsive fluorescence-on probes

pH is critical for diverse physiological activities. Disruption of pH homeostasis is pertinent to myriad pathological events. Particularly, the organelle-specific pH within mammalian cells is elaborately controlled and yet succumbs to pathological stress. Lysosomes are the major intracellular acidic compartments, and the lysosomal acidity is critical for diverse biological events. Aberrant lysosomal pH is manifested a broad spectrum of diseases ranging from inflammation to cancer metastasis, and to lysosomal storage diseases. As such, defining pH changes in specific pathological settings would be of use for biomedical investigations. Rhodamine-lactams, a group of nonfluorescent rhodamine derivatives featuring intramolecular spirolactam, are poised to proton triggered opening of the lactams to give fluorescent rhodamines, and has been widely used for lysosomal imaging in cell models. Herein we review the use of structurally modified rhodamine-lactams as acidity-reporting entities for bioimaging of distinct biological events, including host-pathogen interaction, cell death, autophagy, and mitochondrial depolarization in cells, and inflammation and tumors in mice models.