GABAA Receptor‐Specific Carbon Dots for High‐Contrast Hepatocellular Carcinoma Imaging and Differentiation

Abstract Targeted fluorescence probes for imaging and differentiation of hepatocellular carcinoma (HCC) are highly desirable from its scientific research and clinical applications. However, most of the current targeted fluorescence probes focus on the variation of intracellular microenvironment caused by the cancerization of hepatocyte, which causes a fluorescence intensity alteration but fails to produce a spatial differentiation due to the lack of robust parameters for further improving accuracy. Herein, the study develops a new fluorescent carbon dot (CTF‐CDs) that can target the overexpressed GABA A receptor (GABA A R) on cell membrane for accurate and high‐contrast imaging of HCC and differentiation. The competition response between CTF‐CDs and typical receptor‐binding ligands reveals their affinity toward the picrotoxin‐binding site of GABA A R. Based on this GABA A R‐targeting ability, accurate imaging of HCC cells is realized by lighting their membranes, along with a big difference from the intracellular fluorescence of normal liver cells and other cancer cells. In addition, the CTF‐CDs have also been used to visualize the anticancer drug‐induced variations on HCC cell membrane and fluorescent imaging in HCC tissue. This work extends the targeting object of fluorescence probes from intracellular microenvironment to membrane protein, adding a new dimension to the imaging and differentiation of HCC.