RESUMO
Objective: To investigate the antitumor activity of pH-sensitive liposomes (pH-LPC-lips) loaded with lactosyl-norcantharitin (Lac-NCTD) phospholipids complex in vitro and in vivo, and the liver targeting in mice. Methods: Using blank liposomes (blank-lips and blank-pH-lips) as control, the MTT assay was used to study the cytotoxic effects of Lac-NCTD and its liposomes (Lac-lips and pH-LPC-lips) on human hepatoma carcinoma cells HepG2. HPLC assay was used to evaluate the uptake of Lac-NCTD and its liposomes in HepG2. In vivo antitumor activity of Lac-NCTD and its liposomes were evaluated in mice bearing H22 liver tumors. The hepatocyte specificity of near-infrared fluorescence dye (Cy7)-labeled pH-LPC-lips in H22 tumor-bearing mice was monitored through NIR fluorescence real-time tumor imaging instrument. Results: The pH-LPC-lips demonstrated stronger cytotoxicity against tumor cells HepG2 and easily permeated the cell membrane, compared with Lac-NCTD and Lac-lips. The results of antitumor activity in vivo showed that pH-LPC-lips displayed best tumor inhibitory effect. The optical imaging results indicated that Cy7-labeled pH-LPC-lips showed excellent hepatocyte specificity in H22 tumor-bearing mice, which could reduced the side effect, and increased the antitumor activity. Conclusion: The pH-LPC-lips could take the initiative to release at the tumor site and showed the liver-targeting. As a result, the preparation could be regarded as novel liver-targeting agent which has better antitumor effect.
RESUMO
Objective: To investigate the anticancer activity of the novel lactosyl-norcantharidin nanoparticles (Lac-NCTD-NPs) in vivo and in vitro. Methods: The MTT method was used to study the cytotoxic effects of Lac-NCTD and Lac-NCTD-NPs on HepG2, SMMC-7721, and SGC-7901 cell lines for 12 and 48 h, respectively, and the inhibitory effects of Gal-FBS; Lac-NCTD accumulated in SMMC-7721 cells was assayed by HPLC; The in vivo anticancer activity was evaluated by the tumor-growth inhibition in H22 tumor bearing mice. Results: The in vitro studies showed that the cytotoxic effects of Lac-NCTD-NPs against HepG2 and SMMC-7721 cells were the most powerful, as well as the IC 50 was the lowest, then Lac-NCTD, and they were inhibited remarkably by Gal-FBS; As for SGC-7901 cell line, the cytotoxic effects of Lac-NCTD-NPs and Lac-NCTD were not stronger than that of NCTD, and Gal-FBS had no influence on them at all; The amount of Lac-NCTD accumulated in SMMC-7721 cells was 3. 89 μg (7.02×10-3 μmol, 1×106 cell) after treatment for 12 h; The results of the antitumor activity in vivo suggested that the inhibitory rate of Lac-NCTD-NPs on tumor weight was 63.9%, which was significantly higher than that of NCTD and Lac-NCTD groups at the same molar concentration. Conclusion: The tumor-growth is inhibited effectively by Lac-NCTD-NPs which may be a kind of novel liver-targeting agents and could strongly inhibit the tumor-growth.