A pH‐Responsive Glycyrrhetinic‐Acid‐Modified Small‐Molecule Conjugate for NIR Imaging of Hepatocellular Carcinoma (HCC)

Abstract

We report a glycyrrhetinic‐acid (GA)‐decorated small‐molecule conjugate for pH‐triggered near‐infrared (NIR) fluorescence imaging of hepatocellular carcinoma (HCC). Our in vitro studies demonstrated that the conjugate, referred to as NIR‐GA, was efficiently taken up by liver cancer cell lines such as HepG2 and Huh7 through an endocytic pathway mediated by GA receptors. As suggested by co‐localization studies, NIR‐GA mainly localized in the lysosome, where the acidic pH results in the activation of the fluorescent dye through H+‐triggered spirolactam ring opening to give strong fluorescence in the NIR region.

Glycyrrhetinic Acid-Functionalized Mesoporous Silica Nanoparticles for the Co-Delivery of DOX/CPT-PEG for Targeting HepG2 Cells

“…It is worth noting that even at higher exposure times (24 h), the internalization did not increase, suggesting that the GA receptors were completely saturated, thus preventing endocytosis. Alternatively, this saturation can be induced by addition of an excess amount of GA-CHO (3) [3,17,21]. The internalization of MSNs in HepG2 cells was further studied by confocal laser scanning microscopy (CLSM), labeling the endosomes of the cells with antibody against RAB7, a protein present in late endosomes, for two different periods of time: 1 h ( Figure 6) and 10 h ( Figure S9).…”

“…Up to now, liver transplantation is the preferred choice applied as a treatment, but its application is usually hampered due to the lack of donors. An alternative treatment is the surgical intervention, but it is often too complex due to the inaccessibility of the tumors [2,3]. Therefore, chemotherapy has become the standard of care to fight this malignancy.…”

“…This selectivity can be improved with the installation of ligands on the surface of the NP able to recognize and bind to receptors overexpressed by tumor cells [4,13,18,19]. It has been reported that human hepatocellular carcinoma HepG2 cells possess a significant number of glycyrrhetinic acid (GA) and hyaluronic acid (HA) receptors in its membrane [3,4,17,20]. This feature has been capitalized on the design of selective DDSs and the surface of nanoparticles has been decorated with these ligands to enhance the concentration of the nanocarrier in the tumoral tissue [4,[20][21][22].…”

Fluorescent Probe for Monitoring Hydrogen Peroxide in COX-2-Positive Cancer Cells

“…Targeted fluorescence molecular probes have been developed to explore various biological processes involved in cancer and at cellular levels. − Various fluorescent probes have been developed by several research groups for imaging certain overexpressed enzymes as target for cancer selective imaging. Particularly, quinone oxidoreductase isozyme 1 (NQO1), β-galactosidase, and γ-glutamyltranspeptidase (GGT) has been explored as a target to differentiate cancer cells from normal cells. − Likewise, other chemical events occurring specifically in cancer cells, like acidic pH and overproduction of H 2 O 2 and glutathione, have been explored. − These research efforts have widened the knowledge and ideas for further development of molecular targeted probes.…”

Glycyrrhetinic acid modified and pH-sensitive mixed micelles improve the anticancer effect of curcumin in hepatoma carcinoma cells

“…29,30 In addition, glycyrrhetinic acid (GA), the receptor overexpressed on the surface of hepatoma cells, was also chosen to modify with the F68 polymer with the aim of better tumor targeting. [31][32][33][34][35] Herein, CUR loaded mixed micelles (MIX/CUR) which composed of F68-acetal-PCL (FAP) and F68-GA (FGA) polymers were prepared to attain tumor targeted and acid sensitive goals in this study (Fig. 1).…”