Organelles are dynamic yet highly organized to preserve cellular homeostasis. However, the absence of time-resolved molecular tools for simultaneous dual-signal imaging of two organelles has prevented scientists from elucidating organelle interaction regulatory mechanisms on a nanosecond timescale. To date, the regulatory mechanisms governing the interaction between endoplasmic reticulum (ER) and autophagosomes are unknown. In this study, we propose a strategy for developing dualfluorescence lifetime probes localized to the endoplasmic reticulum and autophagosomes to investigate their interaction regulatory mechanisms. Using the robust probe CF2, we investigated the regulatory mechanisms between ER and autophagosomes and discovered the following: (i) motile autophagosome in ER tips drives the ER tubule to grow and slide; (ii) the ER reticulate tubule forms a three-way junction centered on the autophagosome; (iii) ER autophagy is a type of cell damage index during drug-induced apoptosis. Thus, this study advances our knowledge of organelle interaction regulatory mechanisms, shedding light on the identification of therapeutic targets for neurodegenerative diseases.

Hepatocellular carcinoma is a highly invasive malignant tumor of the liver, which is the main cause of cancer-related death. The cancerization of hepatocytes may lead to the changes of cell microenvironment, active substances, and enzymes. Viscosity is one of the important parameters of cell microenvironment. Therefore, the study of the change in the viscosity of hepatocytes is very important for the detection and treatment of liver cancer. However, the hepatocyte-specific fluorescent probes which can detect viscosity have not been developed yet. Herein, the first hepatocyte-specific fluorescent probe (HT-V) for viscosity detection was designed and synthesized, which exhibited excellent optical properties for biological imaging studies. By using the unique probe HT-V, compared with the normal liver cells, a significant increase of viscosity in the liver cancer cells was observed in the cell imaging experiment. The organ imaging experiments showed that the probe HT-V could be successfully used to diagnose and image hepatocellular carcinoma in vivo. In addition, in situ imaging revealed that the new probe HT-V can specifically target and image hepatocellular carcinoma in mice. We expected that this powerful tool may provide guidance for the detection and imaging of hepatocellular carcinoma in the future.

A new therapeutic probe for detecting and inhibiting ONOO− in senescent cells.

We have designed a new fluorescent probe (HFOAc) for detecting N2H4 in solution, steam, and the biological system.