Visualizing Viscosity Changes in Tumor and Rheumatoid Arthritis with a Dual-Targeted NIR Fluorescent Probe

Targeting mitochondria and nucleus fluorescent probes have emerged as powerful tools for monitoring cellular processes, such as apoptosis and ferroptosis. Nevertheless, only a few near-infrared (NIR) fluorescent probes have been developed for the simultaneous detection of both viscosity and DNA/RNA. Therefore, a mitochondrion- and nucleus-targeted NIR fluorescence probe (BHD) for the detection of viscosity and DNA/RNA was designed and synthesized through the condensation reaction of 1,1,2,3-Tetramethyl-1H-benzo[e]indolium hexafluorophosphate and 4-(dimethylamino)cinnamaldehyde. BHD exhibited remarkable stability under physiological pH and in the presence of biological ions. Due to its cationic structure and strong DNA/RNA binding affinity, BHD was capable of simultaneously targeting both mitochondria and the nucleus. Cellular imaging analysis showed that BHD can effectively detect apoptosis induced by hydrogen peroxide (H₂O₂) and cisplatin. Interestingly, BHD also revealed that the living cells treated with rotenone for a short duration did not undergo an apoptosis process. By monitoring the variation in fluorescence intensity, BHD can efficiently monitor ferroptosis induced by erastin and further showed that Ferrostatin-1 (Fer-1) was able to inhibit this process. Notably, in vivo imaging of viscosity fluctuations associated with tumoral ferroptosis and rheumatoid arthritis (RA) models has been successfully accomplished.