| Abstract: | In our study, a novel hepatocyte-targeting norcantharidin (NCTD) derivative lactosyl-norcantharidin (Lac-NCTD) was synthesised using ethanediamine as a truss arm, and lactosyl-norcantharidin nanoparticles (Lac-NCTD-NPs) were obtained by an ionic cross-linkage process with an entrapment efficiency of (80.29?±?0.56)%. The release of Lac-NCTD-NPs in vitro was then investigated by means of a dialysis method, and its sustained effect was evident. The in vitro anti-tumour activities of Lac-NCTD and Lac-NCTD-NPs were studied by their cytotoxic effects on HepG2, SMMC-7721 and SGC-7901 cells. The results showed that the IC50 values of Lac-NCTD and Lac-NCTD-NPs cytotoxicity against HepG2 and SMMC-7721 cells were lower compared to NCTD, and the anti-tumour effects could be remarkably inhibited by galactosylated fetal bovine serum (Gal-FBS) as a competitor of the asialoglycoprotein receptor. The cytotoxic effects against SGC-7901 cells were relatively high, even higher than NCTD, and Gal-FBS had no influence on them at all. The amount of Lac-NCTD accumulated in SMMC-7721 cells was assayed by high-performance liquid chromatography, which indicated that Lac-NCTD may be able to permeate the cell membrane in its unchanged form. The anti-tumour activities of Lac-NCTD and Lac-NCTD-NPs in vivo were evaluated in mice bearing an H22 tumour. The results suggested that tumour growth was effectively inhibited by all treatments, including NCTD, Lac-NCTD and Lac-NCTD-NPs, with Lac-NCTD-NPs being the most effective, followed by Lac-NCTD. As a result, Lac-NCTD-NPs may be regarded as liver-targeting agents, which combine both active and passive targeting. |
