Facile Way to Differentiate Normal and Cancerous Tissues via Polarity-Sensitive Fluorescent Probes Based on 1,6-Naphthyridine Derivatives

Cancer is a genetic disorder caused by the long-term interaction of many factors, which has become the most important factor to take away human health; therefore, it is essential to develop a more efficient and sensitive cancer detection technology. This study developed two polarity sensitive probes <b>1a</b> and <b>1b</b> based on a 1,6-naphthyridine moiety linked to different targeting groups by vinyl as the π bridge. As the solvent polarity decreased, the emission wavelength of probes <b>1a</b> and <b>1b</b> experienced a blue shift, resulting in a significant enhance in fluorescence intensity by 135-fold and 53-fold, respectively, and a good linear relationship between <i>F</i>_max of probes <b>1a</b> and <b>1b</b> and Δ<i>f</i> was established with high correlation coefficients. Furthermore, probes <b>1a</b> and <b>1b</b> exhibited large Stokes shifts, high photostability, and low cytotoxicity, successfully targeting intracellular lipid droplets and mitochondria. Fluctuation in polarity was detected by real-time changes in fluorescence intensity of probes in lipid droplets and mitochondria. Moreover, probe <b>1b</b> was capable of real-time monitoring mitochondrial polarity during starvation or rapamycin-induced autophagy. It was worth standing out <b>1a</b> and <b>1b</b> could distinguish normal cells from cancer cells, and then the probes also were successfully applied for imaging to differentiate between human normal tissues and cancerous tissues, with the fluorescence intensity of malignant tumor tissues being 15.4-19.9 folds higher than that of normal tissues and 5.3-7.2 times higher than that of benign tumor tissues. Therefore, this research offers potential applications for cancer diagnosis.