Imaging and Detection of Hepatocellular Carcinoma with a Hepatocyte-Specific Fluorescent Probe

Abstract

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.

Near-infrared (NIR) fluorescence-emitting small organic molecules for cancer imaging and therapy

“…234–237 To develop viscosity-sensitive fluorescent probes, researchers have generally utilized ICT-based fluorophores that contain the electron donor-acceptor system. 238–240 Fluorophores in this system display weak fluorescence in low viscosity media ( e.g. , normal tissue environment) due to twisted intramolecular charge transfer (TICT) caused by intramolecular rotation.…”

“…[234][235][236][237] To develop viscosity-sensitive fluorescent probes, researchers have generally utilized ICT-based fluorophores that contain the electron donor-acceptor system. [238][239][240] Fluorophores in this system display weak fluorescence in low viscosity media (e.g., normal tissue environment) due to twisted intramolecular charge transfer (TICT) caused by intramolecular rotation. In contrast, in high viscosity media (e.g., tumor microenvironment), the fluorophores have restricted intramolecular rotation, thereby leading to suppressed TICT and an enhancement of fluorescence emission.…”

Nanotechnology strategies for hepatocellular carcinoma diagnosis and treatment

“…67 In response to the signicantly higher viscosity in hepatocellular carcinoma cells, Li et al developed a uorescent probe specic for hepatocytes (HT-V) that not only allows bioimaging but also sensitively detects differences in viscosity for in vivo diagnosis of HCC. 68 Furthermore, Surface-Enhanced Raman scattering (SERS) has been reported to be more sensitive and photostable than uorescence imaging. The ability of Raman imaging of SERS NPs to detect HCC is more accurate and stable than that of ICG.…”

“… 67 In response to the significantly higher viscosity in hepatocellular carcinoma cells, Li et al developed a fluorescent probe specific for hepatocytes (HT-V) that not only allows bioimaging but also sensitively detects differences in viscosity for in vivo diagnosis of HCC. 68 …”

A NIR Fluorescent Probe Benzopyrylium Perchlorate-based for Visual Sensing and Imaging of SO2 Derivatives in Living Cells

“…Fluorescent probe technology has been proved more practical due to its many outstanding properties such as non-invasive, high temporal resolution, high sensitivity as well as real-time detectability, which are widely used in biochemical analysis, environmental analysis, biological imaging, medical diagnosis and other elds [19][20][21][22][23]. Recently, with regard to SO 2 derivatives determination and recognition, a variety of functional and practical uorescent probes with highly selective and sensitive have been built and these probes have achieved satisfactory results in sensing and uorescence imaging in living cells and in vivo, whose different recognition mechanism mainly including intramolecular charge transfer (ICT) effect, Michael addition, resonance energy transfer (FRET), and nucleophilic addition with aldehyde groups [24][25][26][27][28].…”