Preparation of a novel liver-targeting nanoparticle of norcantharidin derivative and evaluation of its anti-tumour activity

Abstract

2011) Preparation of a novel livertargeting nanoparticle of norcantharidin derivative and evaluation of its anti-tumour activity, 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 AE 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 IC 50 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.

Impact of administration route on nanocarrier biodistribution in a murine colitis model

“…Systemic administration (e.g. intravenous) can transport nanomaterials to intestinal tissues; however, uptake in inflamed tissue derives from vascular permeability rather than specific interstitial cell populations, and the vast majority of material distributes to organs of the mononuclear phagocytotic system (liver and spleen) [ 17 , 20 ].…”