论文部分内容阅读
Purpose: To develop a new liver-targeting drug delivery system (Lactosyl-norcantharidin Ntrimethylchitosan nanoparticles , Lac-NCTD-TMC-Nps ) and confirm its targeting characteristics. Methods: Lac-NCTD-TMC-Nps was prepared by an ionic cross-linkage process. The in vitro antitumor activity and cellular uptake of Lac-NCTD-TMC-Nps to HepG2 cells were studied. The in vivo antitumor activities and tumor-targeting of Lac-NCTD-TMC-Nps were evaluated in mice bearing H22 liver tumors. Results: Lac-NCTD-TMC-Nps were obtained with average particle size of (120.6±1.7)nm, entrapment efficiency of (69.29 ± 0.76)％, and drug-loading amount of (9.1± 0.07)％. In HepG2, the half-maximum inhibiting concentration (IC50) of Lac-NCTD-TMC-Nps was only 24.2％ of that of free Lac-NCTD at 24h. Apoptosis was found as the pathway that Lac-NCTD induced HepG2 cell death. In vitro cellular uptake and in vivo NIR fluorescence realtime imaging both showed the high targeting efficacy. Lac-NCTD-TMC-Nps showed greatest antitumor activity compared with Lac-NCTD and Lactosyl-norcantharidin chitosan nanoparticles (Lac-NCTD-CS-Nps) on the marine hepatocarcinoma 22 subcutaneous model. Conclusions: The Lac-NCTD-TMC-Nps can be regarded as liver-targeting agents that integrates active targeting of Lac-NCTD, charge targeting of TMC , and its own passive targeting function.